Methods and systems for weighting calibration points and updating lag parameters

ABSTRACT

Disclosed are analyte monitoring systems and methods for calibrating an analyte sensor using one or more reference measurements. These systems and methods may include using a conversion function and first sensor data to calculate a first sensor analyte level, weighting a first reference analyte measurement (RM1) and one or more previous reference analyte measurements according to a weighted average cost function, updating the conversion function using the weighted RM1 and the one or more weighted previous reference analyte measurements as calibration points, and using the updated conversion function and second sensor data to calculate a second sensor analyte level. In some aspects, the systems and methods may include updating one or more of lag parameters used to calculate the sensor analyte levels.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of priority to U.S.Provisional Application Ser. No. 62/649,329, filed on Mar. 28, 2018,U.S. Provisional Application Ser. No. 62/566,846, filed on Oct. 2, 2017,and U.S. Provisional Application Ser. No. 62/563,240, filed on Sep. 26,2017, each of which is incorporated herein by reference in theirentireties.

BACKGROUND Field of Invention

The present invention relates to calibrating an analyte sensor of ananalyte monitoring system used to calculate analyte levels in a firstmedium using at least one measurement from a second medium. Morespecifically, aspects of the present invention relate to weightingcalibration points and updating lag parameters at different timeperiods. Even more specifically, aspects of the present invention relateto calculating blood analyte levels using measurements of interstitialfluid analyte levels and one or more of weighted calibration points anddifferent lag parameters for different time periods.

Discussion of the Background

Analyte monitoring systems may be used to measure analyte levels, suchas analyte amounts or concentrations. One type of analyte monitoringsystem is a continuous glucose monitoring (CGM) system. A CGM systemmeasures glucose levels throughout the day and can be very useful in themanagement of diabetes. Some analyte monitoring systems use measurementsindicative of analyte levels in interstitial fluid (“ISF”) to calculateISF analyte levels and then convert the ISF analyte levels to bloodanalyte levels. The analyte monitoring systems may display the bloodanalyte levels to a user. However, because ISF analyte levels lag behindblood analyte levels, accurate conversion of ISF analyte levels to bloodanalyte levels is difficult.

Analyte monitoring systems require calibration (and re-calibration) tomaintain accuracy and sensitivity. The calibration may be, for exampleand without limitation, performed daily or twice-daily. The calibrationmay be performed using one or more reference measurements. The referencemeasurements may be, for example and without limitation, self-monitoringblood glucose (SMBG) measurements. The reference measurements may be,for example and without limitation, obtained from finger-stick bloodsamples.

Improved calibration systems and methods are needed for more accurateanalyte monitoring.

SUMMARY

Aspects of the present invention relate to improving calibrationreliability and analyte measurement accuracy by mitigating the errors inhistorical calibration points and/or to avoid over-fitting the currentcalibration point based on recent calibration points. Aspects of thepresent invention relate to assigning weights to one or more historicalcalibration points in order to avoid over-fitting the calibration pointbased on recent readings and thereby increasing sensor measurementaccuracy. The improvement in sensor measurement accuracy may, forexample and without limitation, limit the number of false alerts relatedto high or low analyte levels, which may be especially helpful overnightwhen a user is trying to sleep.

Aspects of the present invention involve updating one or more parametersused to calculate an analyte level in a first medium using an analytelevel in a second medium. In some embodiments, these parameters may belag parameters that model, for example, diffusion and consumption ratesof an analyte. Updating the lag parameters over time may lead toincreased sensor accuracy because the lag time may change over the lifecycle of the sensor. An aspect of the present invention involvesdetermining whether to update these parameters, for example, based onwhether a period of time has passed since the lag parameters were lastupdated.

One aspect of the invention provides a method of calibrating an analytesensor using one or more reference measurements. The method may includereceiving first sensor data from an analyte sensor. The method mayinclude using a conversion function and the first sensor data tocalculate a first sensor analyte level. The method may include receivinga first reference analyte measurement (RM1). The method may includestoring the RM1 in a calibration point memory that includes one or moreprevious reference analyte measurements. The method may includeweighting the RM1 and the one or more previous reference analytemeasurements according to a weighted average cost function. The methodmay include updating the conversion function using the weighted RM1 andthe one or more weighted previous reference analyte measurements ascalibration points. The method may include receiving second sensor datafrom the analyte sensor. The method may include using the updatedconversion function and the second sensor data to calculate a secondsensor analyte level.

In some embodiments, the RM1 may be a self-monitoring blood glucose(SMBG) measurement obtained from a finger-stick blood sample. In someembodiments, the calibration point memory may be a circular buffer.

In some embodiments, the weightings for the weighted RM1 and the one ormore weighted previous reference analyte measurements may be calculatedusing an exponential growth formula. In some embodiments, theexponential growth formula may include a growth parameter α defined as

${\alpha = \left( \frac{t_{i} - t_{0}}{\lambda} \right)},$t₀ may be the time stamp of the current calibration point, i may equal−(N−1), −(N−2), . . . 0, N may be the number of calibration points, andλ, may be the relative time difference between the current and theprevious calibration points. In some embodiments, N may be a constantvalue. In some embodiments, λ, may be a constant value.

In some embodiments, the weighted average cost function may include anaccuracy metric, Error(θ)_(i).

In some embodiments, the calculated first sensor analyte level may be alevel of analyte in a first medium, and the first sensor data maycomprise one or more measurements of an analyte level in a secondmedium. In some embodiments, the first medium may be blood, and thesecond medium may be interstitial fluid. In some embodiments, using theconversion function and the first sensor data used to calculate thefirst sensor analyte measurement may include: calculating a secondmedium analyte level using at least the first sensor data, calculating asecond medium level rate of change using at least the second mediumanalyte level, and calculating the first sensor analyte level using atleast the second medium analyte level and the second medium level rateof change. In some embodiments, the first sensor analyte level may becalculated using at least the second medium analyte level, the secondmedium level rate of change, and one or more lag parameters. In someembodiments, the one or more lag parameters may include one or more ofan analyte diffusion rate and an analyte consumption rate.

In some embodiments, the method may further include determining whetherto update one or more of the lag parameters. In some embodiments, themethod may further include updating one or more of the lag parameters.In some embodiments, determining whether to update one or more of thelag parameters may include determining whether a period of time haspassed since the one or more of the lag parameters has been updated.

In some embodiments, the method may further include updating one or moreof the lag parameters. In some embodiments, updating one or more lagparameters may include using one or more of a first method and a secondmethod to estimate one or more updated lag parameters. In someembodiments, the first method may be a ratio method. In someembodiments, the second method may be a two-parameter method. In someembodiments, updating one or more lag parameters may include using thefirst method during a first period and using the second method during asecond period. In some embodiments, updating one or more lag parametersmay include using both the first and second methods. In someembodiments, using both the first and second methods may include usingthe first method to estimate a first set of updated lag parameters. Insome embodiments, using both the first and second methods may includeusing the second method to estimate a second set of updated lagparameters. In some embodiments, using both the first and second methodsmay include using the first set of updated lag parameters to calculateone or more first sensor measurements. In some embodiments, using boththe first and second methods may include using the second set of updatedlag parameters to calculate one or more second sensor measurements. Insome embodiments, using both the first and second methods may includeevaluating the one or more first sensor measurements and the one or moresecond sensor measurements by comparing the one or more first sensormeasurements and the one or more second sensor measurements to one ormore reference measurements. In some embodiments, using both the firstand second methods may include selecting the more accurate of (a) theone or more first sensor measurements and (b) the one or more secondsensor measurements for display to a user.

In some embodiments, the first sensor analyte level may be calculatedusing a two-compartment model that models the transport of the analytefrom the first medium and in the second medium. In some embodiments, thetwo-compartment model may be

${\frac{{dC}_{2}}{dt} = {{p_{2}*\left\lbrack {{C_{1}(t)} - {C_{2}(t)}} \right\rbrack} - {p_{3}*{C_{2}(t)}}}},$where C₁(t) may be a concentration of the analyte in the first medium,C₂(t) may be a concentration of the analyte in the second medium, p2 maybe an analyte diffusion rate, and p3 may be an analyte consumption rate.In some embodiments, 1/p₂ and p₃/p₂ may be lag parameters.

In some embodiments, the method may further include determining whetherto dynamically update one or more of the lag parameters. In someembodiments, the method may further include dynamically updating one ormore of the lag parameters. In some embodiments, dynamically updatingone or more of the lag parameters may include using a minimum deviationdivergence method.

In some embodiments, the conversion function may employ an asymmetricallag methodology. In some embodiments, the asymmetrical lag approach maydecelerate a rate of change of falling glucose levels during a low bloodglucose event and accelerates a rate of change of increasing glucoselevels during recovery from the low blood glucose event.

Another aspect of the invention provides an analyte monitoring systemincluding an analyte sensor and a transceiver. The analyte sensor mayinclude an indicator element that exhibits one or more detectableproperties based on a concentration of an analyte in proximity to theindicator element. The transceiver may be configured to receive firstsensor data from the analyte sensor. The transceiver may be configuredto use a conversion function and the first sensor data to calculate afirst sensor analyte level. The transceiver may be configured to receivea first reference analyte measurement (RM1). The transceiver may beconfigured to store the RMI in a calibration point memory that includesone or more previous reference analyte measurements. The transceiver maybe configured to weight the RM1 and the one or more previous referenceanalyte measurements according to a weighted average cost function. Thetransceiver may be configured to update the conversion function usingthe weighted RM1 and the one or more weighted previous reference analytemeasurements as calibration points. The transceiver may be configured toreceive second sensor data from the analyte sensor. The transceiver maybe configured to use the updated conversion function and the secondsensor data to calculate a second sensor analyte level.

In some embodiments, the RM1 may be a self-monitoring blood glucose(SMBG) measurement obtained from a finger-stick blood sample. In someembodiments, the calibration point memory may be a circular buffer.

In some embodiments, the weightings for the weighted RM1 and the one ormore weighted previous reference analyte measurements may be calculatedusing an exponential growth formula. In some embodiments, theexponential growth formula may include a growth parameter α defined as

${\alpha = \left( \frac{t_{i} - t_{0}}{\lambda} \right)},$t₀ may be the time stamp of the current calibration point, i may equal−(N−1), −(N−2), . . . 0, N may be the number of calibration points, andλ may be the relative time difference between the current and theprevious calibration points. In some embodiments, N may be a constantvalue. In some embodiments, λ may be a constant value.

In some embodiments, the weighted average cost function may include anaccuracy metric, Error(θ)_(i). In some embodiments, the calculated firstsensor analyte level may be a level of the analyte in a first medium,and the first sensor data may include one or more measurements of theanalyte level in a second medium. In some embodiments, the first mediummay be blood, and the second medium may be interstitial fluid.

In some embodiments, the transceiver may be further configured to:calculate a second medium analyte level using at least the first sensordata, calculate a second medium level rate of change using at least thesecond medium analyte level, and calculate the first sensor analytelevel using at least the second medium analyte level and the secondmedium level rate of change. In some embodiments, the first sensoranalyte level may be calculated using at least the second medium analytelevel, the second medium level rate of change, and one or more lagparameters. In some embodiments, the one or more lag parameters mayinclude one or more of an analyte diffusion rate and an analyteconsumption rate. In some embodiments, the transceiver may be furtherconfigured to determine whether to update one or more of the lagparameters. In some embodiments, the transceiver may be furtherconfigured to update one or more of the lag parameters. In someembodiments, determining whether to update one or more of the lagparameters may include determining whether a period of time has passedsince the one or more of the lag parameters has been updated.

In some embodiments, the transceiver may be further configured to updateone or more of the lag parameters. In some embodiments, updating one ormore lag parameters may include using one or more of a first method anda second method to estimate one or more updated lag parameters. In someembodiments, the first method may be a ratio method. In someembodiments, the second method may be a two-parameter method. In someembodiments, updating one or more lag parameters may include using thefirst method during a first period and using the second method during asecond period. In some embodiments, updating one or more lag parametersmay include using both the first and second methods. In someembodiments, using both the first and second methods may include one ormore of: using the first method to estimate a first set of updated lagparameters; using the second method to estimate a second set of updatedlag parameters; using the first set of updated lag parameters tocalculate one or more first sensor measurements; using the second set ofupdated lag parameters to calculate one or more second sensormeasurements; evaluating the one or more first sensor measurements andthe one or more second sensor measurements by comparing the one or morefirst sensor measurements and the one or more second sensor measurementsto one or more reference measurements; and selecting the more accurateof (a) the one or more first sensor measurements and (b) the one or moresecond sensor measurements for display to a user.

In some embodiments, the first sensor analyte level may be calculatedusing a two-compartment model that models the transport of the analytefrom the first medium and in the second medium. In some embodiments, thetwo-compartment model may be

${\frac{{dC}_{2}}{dt} = {{p_{2}*\left\lbrack {{C_{1}(t)} - {C_{2}(t)}} \right\rbrack} - {p_{3}*{C_{2}(t)}}}},$C₁(t) may be a concentration of the analyte in the first medium, C₂(t)may be a concentration of the analyte in the second medium, p2 may be ananalyte diffusion rate, and p3 may be an analyte consumption rate. Insome embodiments, 1/p₂ and p₃/p₂ may be lag parameters.

In some embodiments, the transceiver may be further configured todetermine whether to dynamically update one or more of the lagparameters. In some embodiments, the transceiver may be furtherconfigured to dynamically update one or more of the lag parameters. Insome embodiments, dynamically updating one or more of the lag parametersmay include using a minimum deviation divergence method.

In some embodiments, the conversion function may employ an asymmetricallag methodology. In some embodiments, the asymmetrical lag approach maydecelerate a rate of change of falling glucose levels during a low bloodglucose event and accelerate a rate of change of increasing glucoselevels during recovery from the low blood glucose event.

Still another aspect of the invention provides a method of calculatingan analyte level in a first medium using one or more measurements of ananalyte level in a second medium. The method may include receiving firstsensor data from an analyte sensor. The method may include calculating afirst analyte level in the second medium using at least the first sensordata. The method may include calculating a first analyte level rate ofchange using at least the first analyte level in the second medium. Themethod may include calculating a first analyte level in the first mediumusing at least the first analyte level in the second medium, the firstanalyte level rate of change, and one or more lag parameters. The methodmay include determining that the one or more lag parameters should beupdated. The method may include updating the one or more lag parameters.The method may include receiving second sensor data from the analytesensor. The method may include calculating a second analyte level in thesecond medium using at least the second sensor data. The method mayinclude calculating a second analyte level rate of change using at leastthe second analyte level in the second medium. The method may includecalculating a second analyte level in the first medium using at leastthe second analyte level in the second medium, the second analyte levelrate of change, and the updated one or more lag parameters.

In some embodiments, the one or more lag parameters may include one ormore of an analyte diffusion rate and an analyte consumption rate. Insome embodiments, determining that the one or more lag parameters shouldbe updated may include determining that a period of time has passedsince the one or more of the lag parameters has been updated. In someembodiments, the first medium may be blood, and the second medium may beinterstitial fluid.

In some embodiments, the method may further include determining whetherto dynamically update one or more of the lag parameters. In someembodiments, the method may further include dynamically updating one ormore of the lag parameters. In some embodiments, dynamically updatingone or more of the lag parameters may include using a minimum deviationdivergence method.

In some embodiments, calculating the first analyte level in the firstmedium may include employing an asymmetrical lag methodology. In someembodiments, the asymmetrical lag approach may decelerate a rate ofchange of falling glucose levels during a low blood glucose event andaccelerate a rate of change of increasing glucose levels during recoveryfrom the low blood glucose event.

In some embodiments, updating one or more lag parameters may includeusing one or more of a first method and a second method to estimate oneor more updated lag parameters. In some embodiments, the first methodmay be a ratio method. In some embodiments, the second method may be atwo-parameter method. In some embodiments, updating one or more lagparameters may include using the first method during a first period andusing the second method during a second period. In some embodiments,updating one or more lag parameters may include using both the first andsecond methods. In some embodiments, using both the first and secondmethods may include one or more of: using the first method to estimate afirst set of updated lag parameters; using the second method to estimatea second set of updated lag parameters; using the first set of updatedlag parameters to calculate one or more first sensor measurements; usingthe second set of updated lag parameters to calculate one or more secondsensor measurements; evaluating the one or more first sensormeasurements and the one or more second sensor measurements by comparingthe one or more first sensor measurements and the one or more secondsensor measurements to one or more reference measurements; and selectingthe more accurate of (a) the one or more first sensor measurements and(b) the one or more second sensor measurements for display to a user.

Yet another aspect of the invention provides an analyte monitoringsystem including an analyte sensor and a transceiver. The analyte sensormay include an indicator element that exhibits one or more detectableproperties based on a concentration of an analyte in proximity to theindicator element. The transceiver may be configured to receive firstsensor data from the analyte sensor. The transceiver may be configuredto calculate a first analyte level in the second medium using at leastthe first sensor data. The transceiver may be configured to calculate afirst analyte level rate of change using at least the first analytelevel in the second medium. The transceiver may be configured tocalculate a first analyte level in the first medium using at least thefirst analyte level in the second medium, the first analyte level rateof change, and one or more lag parameters. The transceiver may beconfigured to determine that the one or more lag parameters should beupdated. The transceiver may be configured to update the one or more lagparameters. The transceiver may be configured to receive second sensordata from the analyte sensor. The transceiver may be configured tocalculate a second analyte level in the second medium using at least thesecond sensor data. The transceiver may be configured to calculate asecond analyte level rate of change using at least the second analytelevel in the second medium. The transceiver may be configured tocalculate a second analyte level in the first medium using at least thesecond analyte level in the second medium, the second analyte level rateof change, and the updated one or more lag parameters.

In some embodiments, the one or more lag parameters may include one ormore of an analyte diffusion rate and an analyte consumption rate. Insome embodiments, determining that the one or more lag parameters shouldbe updated may include determining that a period of time has passedsince the one or more of the lag parameters has been updated. In someembodiments, the first medium may be blood, and the second medium may beinterstitial fluid.

In some embodiments, the transceiver may be further configured todetermine whether to dynamically update one or more of the lagparameters. In some embodiments, the transceiver may be furtherconfigured to dynamically update one or more of the lag parameters. Insome embodiments, dynamically updating one or more of the lag parametersmay include using a minimum deviation divergence method.

In some embodiments, the transceiver may be further configured todynamically update one or more of the lag parameters. In someembodiments, calculating the first analyte level in the first medium mayinclude employing an asymmetrical lag methodology. In some embodiments,the asymmetrical lag approach may decelerate a rate of change of fallingglucose levels during a low blood glucose event and accelerate a rate ofchange of increasing glucose levels during recovery from the low bloodglucose event.

In some embodiments, updating one or more lag parameters may includeusing one or more of a first method and a second method to estimate oneor more updated lag parameters. In some embodiments, the first methodmay be a ratio method. In some embodiments, the second method may be atwo-parameter method. In some embodiments, updating one or more lagparameters may include using the first method during a first period andusing the second method during a second period. In some embodiments,updating one or more lag parameters may include using both the first andsecond methods. In some embodiments, using both the first and secondmethods may include one or more of: using the first method to estimate afirst set of updated lag parameters; using the second method to estimatea second set of updated lag parameters; using the first set of updatedlag parameters to calculate one or more first sensor measurements; usingthe second set of updated lag parameters to calculate one or more secondsensor measurements; evaluating the one or more first sensormeasurements and the one or more second sensor measurements by comparingthe one or more first sensor measurements and the one or more secondsensor measurements to one or more reference measurements; and selectingthe more accurate of (a) the one or more first sensor measurements and(b) the one or more second sensor measurements for display to a user.

Another aspect of the invention may provide a method of calculating ananalyte level in a first medium using one or more measurements of ananalyte level in a second medium. The method may include receiving firstsensor data from an analyte sensor. The method may include calculating afirst analyte level in the second medium using at least the first sensordata. The method may include calculating a first analyte level rate ofchange using at least the first analyte level in the second medium. Themethod may include calculating a first analyte level in the first mediumusing at least the first analyte level in the second medium, the firstanalyte level rate of change, and a first set of one or more lagparameters. The method may include calculating a second analyte level inthe first medium using at least the first analyte level in the secondmedium, the first analyte level rate of change, and a second set of oneor more lag parameters. The method may include comparing the firstanalyte level in the first medium to at least a reference measurement.The method may include comparing the second analyte level in the firstmedium to at least the reference measurement. The method may includeselecting whichever of the first analyte level in the first medium andthe second analyte level in the first medium is closer to the referencemeasurement for display to a user.

Another aspect of the invention may provide an analyte sensor and atransceiver. The analyte sensor may include an indicator element thatexhibits one or more detectable properties based on a concentration ofan analyte in proximity to the indicator element. The transceiver may beconfigured to receive first sensor data from the analyte sensor. Thetransceiver may be configured to calculate a first analyte level in thesecond medium using at least the first sensor data. The transceiver maybe configured to calculate a first analyte level rate of change using atleast the first analyte level in the second medium. The transceiver maybe configured to calculate a first analyte level in the first mediumusing at least the first analyte level in the second medium, the firstanalyte level rate of change, and a first set of one or more lagparameters. The transceiver may be configured to calculate a secondanalyte level in the first medium using at least the first analyte levelin the second medium, the first analyte level rate of change, and asecond set of one or more lag parameters. The transceiver may beconfigured to compare the first analyte level in the first medium to atleast a reference measurement. The transceiver may be configured tocompare the second analyte level in the first medium to at least thereference measurement. The transceiver may be configured to selectwhichever of the first analyte level in the first medium and the secondanalyte level in the first medium is closer to the reference measurementfor display to a user.

Another aspect of the invention may provide a method including receivingfirst sensor data from an analyte sensor. The method may include using aconversion function and at least the first sensor data to calculate afirst sensor analyte level. The method may include receiving secondsensor data from the analyte sensor. The method may include using theconversion function and at least the second sensor data to calculate asecond sensor analyte level. The method may include receiving a firstreference analyte measurement (RM1). The RM1 may have a time stamp inbetween time stamps of the first and second sensor analyte levels. Themethod may include updating the conversion function using at least theRM1 as a calibration point. Updating the conversion function may includeinterpolating a sensor analyte level having a time stamp that matchesthe time stamp of the RM1 using at least the first and second sensoranalyte levels and the time stamps of the first and second sensoranalyte levels. Updating the conversion function may include pairing theRM1 with the interpolated sensor analyte level. Updating the conversionfunction may include using the pairing of the RM1 with the interpolatedsensor analyte value to update the conversion function. The method mayinclude receiving third sensor data from the analyte sensor. The methodmay include using the updated conversion function to calculate a thirdsensor analyte level.

In some embodiments, interpolating the sensor analyte level having thetime stamp that matches the time stamp of the RM1 may use linearinterpolation. In some embodiments, interpolating the sensor analytelevel having the time stamp that matches the time stamp of the RM1 mayuse polynomial interpolation. In some embodiments, interpolating thesensor analyte level having the time stamp that matches the time stampof the RM1 may use spline interpolation. In some embodiments, the RM1may be a self-monitoring blood glucose (SMBG) measurement obtained froma finger-stick blood sample.

In some embodiments, the conversion function may employ an asymmetricallag methodology. In some embodiments, the asymmetrical lag approach maydecelerate a rate of change of falling glucose levels during a low bloodglucose event and accelerate a rate of change of increasing glucoselevels during recovery from the low blood glucose event.

Yet another aspect of the invention may provide an analyte monitoringsystem including an analyte sensor and a transceiver. The analyte sensormay include an indicator element that exhibits one or more detectableproperties based on a concentration of an analyte in proximity to theindicator element. The transceiver may be configured to receive firstsensor data from the analyte sensor. The transceiver may be configuredto use a conversion function and at least the first sensor data tocalculate a first sensor analyte level. The transceiver may beconfigured to receive second sensor data from the analyte sensor. Thetransceiver may be configured to use the conversion function and atleast the second sensor data to calculate a second sensor analyte level.The transceiver may be configured to receive a first reference analytemeasurement (RM1). The RM1 may have a time stamp in between time stampsof the first and second sensor analyte levels. The transceiver may beconfigured to update the conversion function using at least the RM1 as acalibration point. Updating the conversion function may includeinterpolating a sensor analyte level having a time stamp that matchesthe time stamp of the RM1 using at least the first and second sensoranalyte levels and the time stamps of the first and second sensoranalyte levels. Updating the conversion function may include pairing theRM1 with the interpolated sensor analyte level. Updating the conversionfunction may include using the pairing of the RM1 with the interpolatedsensor analyte value to update the conversion function. The transceivermay be configured to receive third sensor data from the analyte sensor.The transceiver may be configured to use the updated conversion functionto calculate a third sensor analyte level.

In some embodiments, the transceiver may be configured to interpolatethe sensor analyte level having the time stamp that matches the timestamp of the RM1 using linear interpolation. In some embodiments, thetransceiver may be configured to interpolate the sensor analyte levelhaving the time stamp that matches the time stamp of the RM1 usingpolynomial interpolation. In some embodiments, the transceiver may beconfigured to interpolate the sensor analyte level having the time stampthat matches the time stamp of the RM1 using spline interpolation. Insome embodiments, the RM1 may be a self-monitoring blood glucose (SMBG)measurement obtained from a finger-stick blood sample.

In some embodiments, the conversion function may employ an asymmetricallag methodology. In some embodiments, the asymmetrical lag approach maydecelerate a rate of change of falling glucose levels during a low bloodglucose event and accelerate a rate of change of increasing glucoselevels during recovery from the low blood glucose event.

Still another aspect of the invention may provide a method includingusing a display device to prompt a user to enter a referencemeasurement. The method may include using the display device to receivea reference measurement. The method may include using the display deviceto prompt a user to enter a time at which the reference measurement wastaken. The method may include using the display device to receive a timeat which the reference measurement was taken. The method may includeusing the display device to display an analyte level.

In some embodiments, the reference measurement may be a self-monitoringblood glucose (SMBG) measurement obtained from a finger-stick bloodsample.

In some embodiments, the method may further include using the displaydevice to convey the received reference measurement and the receivedtime to a transceiver and may include using the display device toreceive the analyte level from the transceiver. In some embodiments, themethod may further include one or more of: using the transceiver toreceive sensor data from an analyte sensor; using the transceiver tocalculate the analyte level using a conversion function and the sensordata; and using the transceiver to convey the analyte level to thedisplay device. In some embodiments, the method may further include oneor more of: using the transceiver to receive the reference measurementand the time at which the reference measurement was taken; and using thetransceiver to update the conversion function using the referencemeasurement and the time at which the reference measurement was taken.In some embodiments, the method may further include storing thereference measurement in a calibration point memory. In someembodiments, the sensor data may be first sensor data, the analyte levelmay be a first analyte level, and the method further include one or moreof: using the transceiver to receive second sensor data from the analytesensor; using the transceiver to calculate a second sensor analyte levelusing the updated conversion function and the second sensor data; andusing the transceiver to convey the second analyte level to the displaydevice. In some embodiments, the method may further include using thedisplay device to receive the second analyte level from the transceiverand using the display device to display the second analyte level.

Yet another aspect of the invention may provide an analyte monitoringsystem include a transceiver and a display device. The transceiver maybe configured to convey an analyte level. The display device may beconfigured to: prompt a user to enter a reference measurement, receive areference measurement, prompt a user to enter a time at which thereference measurement was taken, receive a time at which the referencemeasurement was taken, receive the analyte level from the transceiver,and display the analyte level.

In some embodiments, the reference measurement may be a self-monitoringblood glucose (SHBG) measurement obtained from a finger-stick bloodsample.

In some embodiments, the display device may be further configured toconvey the received reference measurement and the received time to thetransceiver. In some embodiments, the analyte monitoring system mayfurther include an analyte sensor, and the transceiver may be furtherconfigured to: receive sensor data from the analyte sensor, calculatethe analyte level using a conversion function and the sensor data, andconvey the analyte level to the display device. In some embodiments, thetransceiver may be further configured to: receive the referencemeasurement and the time at which the reference measurement was takenfrom the display device, and update the conversion function using thereference measurement and the time at which the reference measurementwas taken. In some embodiments, the transceiver may be furtherconfigured to store the reference measurement in a calibration pointmemory. In some embodiments, the sensor data may be first sensor data,the analyte level may be a first analyte level, and the transceiver maybe further configured to: receive second sensor data from the analytesensor, calculate a second sensor analyte level using the updatedconversion function and the second sensor data, and convey the secondanalyte level to the display device. In some embodiments, the displaydevice may be further configured to: receive the second analyte levelfrom the transceiver, and display the second analyte level.

Another aspect of the invention may provide a display device including atransceiver interface, a user interface, and a computer. The transceiverinterface may be configured to receive an analyte level from atransceiver. The computer may include a non-transitory memory and aprocessor. The computer may be configured to (i) cause the userinterface to display the analyte level, (ii) cause the user interface toprompt a user to enter a reference measurement, (iii) receive areference measurement entered using the user interface, (iv) cause theuser interface to prompt a user to enter a time at which the referencemeasurement was taken, and (v) receive a time at which the referencemeasurement was taken. The received time may have been entered using theuser interface.

In some embodiments, the reference measurement may be a self-monitoringblood glucose (SHBG) measurement obtained from a finger-stick bloodsample. In some embodiments, the computer may be further configured tocause the transceiver interface to convey the received referencemeasurement and the received time to the transceiver. In someembodiments, the transceiver interface may include an antenna.

Further variations encompassed within the systems and methods aredescribed in the detailed description of the invention below.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated herein and form partof the specification, illustrate various, non-limiting embodiments ofthe present invention. In the drawings, like reference numbers indicateidentical or functionally similar elements.

FIG. 1 is a schematic view illustrating an analyte monitoring systemembodying aspects of the present invention.

FIG. 2 is a schematic view illustrating a sensor and transceiver of ananalyte monitoring system embodying aspects of the present invention.

FIG. 3 is cross-sectional, perspective view of a transceiver embodyingaspects of the invention.

FIG. 4 is an exploded, perspective view of a transceiver embodyingaspects of the invention.

FIG. 5 is a schematic view illustrating a transceiver embodying aspectsof the present invention.

FIG. 6 illustrates a block diagram of a display device of the analytemonitoring system according to some embodiments.

FIG. 7 illustrates a block diagram of a computer of the display deviceof the analyte monitoring system according to some embodiments.

FIG. 8 is a flow chart illustrating a process for controllinginitialization and calibration of an analyte monitoring system embodyingaspects of the present invention.

FIG. 9 is a flow chart illustrating a calibration process embodyingaspects of the present invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1 is a schematic view of an exemplary analyte monitoring system 50embodying aspects of the present invention. The analyte monitoringsystem 50 may be a continuous analyte monitoring system (e.g., acontinuous glucose monitoring system). In some embodiments, the analytemonitoring system 50 may include one or more of an analyte sensor 100, atransceiver 101, and a display device 105. In some embodiments, thesensor 100 may be small, fully subcutaneously implantable sensor thatmeasures analyte (e.g., glucose) levels in a medium (e.g., interstitialfluid) of a living animal (e.g., a living human). However, this is notrequired, and, in some alternative embodiments, the sensor 100 may be apartially implantable (e.g., transcutaneous) sensor or a fully externalsensor. In some embodiments, the transceiver 101 may be an externallyworn transceiver (e.g., attached via an armband, wristband, waistband,or adhesive patch). In some embodiments, the transceiver 101 mayremotely power and/or communicate with the sensor to initiate andreceive the measurements (e.g., via near field communication (NFC)).However, this is not required, and, in some alternative embodiments, thetransceiver 101 may power and/or communicate with the sensor 100 via oneor more wired connections. In some non-limiting embodiments, thetransceiver 101 may be a smartphone (e.g., an NFC-enabled smartphone).In some embodiments, the transceiver 101 may communicate information(e.g., one or more analyte levels) wirelessly (e.g., via a Bluetooth™communication standard such as, for example and without limitationBluetooth Low Energy) to a hand held application running on a displaydevice 105 (e.g., smartphone). In some embodiments, the analytemonitoring system 50 may include a web interface for plotting andsharing of uploaded data.

In some embodiments, as illustrated in FIG. 2, the transceiver 101 mayinclude an inductive element 103, such as, for example, a coil. Thetransceiver 101 may generate an electromagnetic wave or electrodynamicfield (e.g., by using a coil) to induce a current in an inductiveelement 114 of the sensor 100, which powers the sensor 100. Thetransceiver 101 may also convey data (e.g., commands) to the sensor 100.For example, in a non-limiting embodiment, the transceiver 101 mayconvey data by modulating the electromagnetic wave used to power thesensor 100 (e.g., by modulating the current flowing through a coil 103of the transceiver 101). The modulation in the electromagnetic wavegenerated by the transceiver 101 may be detected/extracted by the sensor100. Moreover, the transceiver 101 may receive sensor data (e.g.,measurement information) from the sensor 100. For example, in anon-limiting embodiment, the transceiver 101 may receive sensor data bydetecting modulations in the electromagnetic wave generated by thesensor 100, (e.g., by detecting modulations in the current flowingthrough the coil 103 of the transceiver 101).

The inductive element 103 of the transceiver 101 and the inductiveelement 114 of the sensor 100 may be in any configuration that permitsadequate field strength to be achieved when the two inductive elementsare brought within adequate physical proximity.

In some non-limiting embodiments, as illustrated in FIG. 2, the sensor100 may be encased in a sensor housing 102 (e.g., body, shell, capsule,or encasement), which may be rigid and biocompatible. The sensor 100 mayinclude an analyte indicator element 106, such as, for example, apolymer graft coated, diffused, adhered, or embedded on or in at least aportion of the exterior surface of the sensor housing 102. The analyteindicator element 106 (e.g., polymer graft) of the sensor 100 mayinclude indicator molecules 104 (e.g., fluorescent indicator molecules)exhibiting one or more detectable properties (e.g., optical properties)based on the amount or concentration of the analyte in proximity to theanalyte indicator element 106. In some embodiments, the sensor 100 mayinclude a light source 108 that emits excitation light 329 over a rangeof wavelengths that interact with the indicator molecules 104. Thesensor 100 may also include one or more photodetectors 224, 226 (e.g.,photodiodes, phototransistors, photoresistors, or other photosensitiveelements). The one or more photodetectors (e.g., photodetector 224) maybe sensitive to emission light 331 (e.g., fluorescent light) emitted bythe indicator molecules 104 such that a signal generated by aphotodetector (e.g., photodetector 224) in response thereto isindicative of the level of emission light 331 of the indicator moleculesand, thus, the amount or concentration of the analyte of interest (e.g.,glucose). In some non-limiting embodiments, one or more of thephotodetectors (e.g., photodetector 226) may be sensitive to excitationlight 329 that is reflected from the analyte indicator element 106 asreflection light 333. In some non-limiting embodiments, one or more ofthe photodetectors may be covered by one or more filters that allow onlya certain subset of wavelengths of light to pass through (e.g., a subsetof wavelengths corresponding to emission light 331 or a subset ofwavelengths corresponding to reflection light 333) and reflect theremaining wavelengths. In some non-limiting embodiments, the sensor 100may include a temperature transducer 670. In some non-limitingembodiments, the sensor 100 may include a drug-eluting polymer matrixthat disperses one or more therapeutic agents (e.g., ananti-inflammatory drug).

In some embodiments, as illustrated in FIG. 2, the sensor 100 mayinclude a substrate 116. In some embodiments, the substrate 116 may be acircuit board (e.g., a printed circuit board (PCB) or flexible PCB) onwhich circuit components (e.g., analog and/or digital circuitcomponents) may be mounted or otherwise attached. However, in somealternative embodiments, the substrate 116 may be a semiconductorsubstrate having circuitry fabricated therein. The circuitry may includeanalog and/or digital circuitry. Also, in some semiconductor substrateembodiments, in addition to the circuitry fabricated in thesemiconductor substrate, circuitry may be mounted or otherwise attachedto the semiconductor substrate 116. In other words, in somesemiconductor substrate embodiments, a portion or all of the circuitry,which may include discrete circuit elements, an integrated circuit(e.g., an application specific integrated circuit (ASIC)) and/or otherelectronic components (e.g., a non-volatile memory), may be fabricatedin the semiconductor substrate 116 with the remainder of the circuitryis secured to the semiconductor substrate 116 and/or a core (e.g.,ferrite core) for the inductive element 114. In some embodiments, thesemiconductor substrate 116 and/or a core may provide communicationpaths between the various secured components.

In some embodiments, the one or more of the sensor housing 102, analyteindicator element 106, indicator molecules 104, light source 108,photodetectors 224, 226, temperature transducer 670, substrate 116, andinductive element 114 of sensor 100 may include some or all of thefeatures described in one or more of U.S. application Ser. No.13/761,839, filed on Feb. 7, 2013, U.S. application Ser. No. 13/937,871,filed on Jul. 9, 2013, and U.S. application Ser. No. 13/650,016, filedon Oct. 11, 2012, all of which are incorporated by reference in theirentireties. Similarly, the structure and/or function of the sensor 100and/or transceiver 101 may be as described in one or more of U.S.application Ser. Nos. 13/761,839, 13/937,871, and 13/650,016.

Although in some embodiments, as illustrated in FIG. 2, the sensor 100may be an optical sensor, this is not required, and, in one or morealternative embodiments, sensor 100 may be a different type of analytesensor, such as, for example, an electrochemical sensor, a diffusionsensor, or a pressure sensor. Also, although in some embodiments, asillustrated in FIGS. 1 and 2, the analyte sensor 100 may be a fullyimplantable sensor, this is not required, and, in some alternativeembodiments, the sensor 100 may be a transcutaneous sensor having awired connection to the transceiver 101. For example, in somealternative embodiments, the sensor 100 may be located in or on atranscutaneous needle (e.g., at the tip thereof). In these embodiments,instead of wirelessly communicating using inductive elements 103 and114, the sensor 100 and transceiver 101 may communicate using one ormore wires connected between the transceiver 101 and the transceivertranscutaneous needle that includes the sensor 100. For another example,in some alternative embodiments, the sensor 100 may be located in acatheter (e.g., for intravenous blood glucose monitoring) and maycommunicate (wirelessly or using wires) with the transceiver 101.

In some embodiments, the sensor 100 may include a transceiver interfacedevice. In some embodiments where the sensor 100 includes an antenna(e.g., inductive element 114), the transceiver interface device mayinclude the antenna (e.g., inductive element 114) of sensor 100. In someof the transcutaneous embodiments where there exists a wired connectionbetween the sensor 100 and the transceiver 101, the transceiverinterface device may include the wired connection.

FIGS. 3 and 4 are cross-sectional and exploded views, respectively, of anon-limiting embodiment of the transceiver 101, which may be included inthe analyte monitoring system illustrated in FIG. 1. As illustrated inFIG. 4, in some non-limiting embodiments, the transceiver 101 mayinclude a graphic overlay 204, front housing 206, button 208, printedcircuit board (PCB) assembly 210, battery 212, gaskets 214, antenna 103,frame 218, reflection plate 216, back housing 220, ID label 222, and/orvibration motor 928. In some non-limiting embodiments, the vibrationmotor 928 may be attached to the front housing 206 or back housing 220such that the battery 212 does not dampen the vibration of vibrationmotor 928. In a non-limiting embodiment, the transceiver electronics maybe assembled using standard surface mount device (SMD) reflow and soldertechniques. In one embodiment, the electronics and peripherals may beput into a snap together housing design in which the front housing 206and back housing 220 may be snapped together. In some embodiments, thefull assembly process may be performed at a single external electronicshouse. However, this is not required, and, in alternative embodiments,the transceiver assembly process may be performed at one or moreelectronics houses, which may be internal, external, or a combinationthereof. In some embodiments, the assembled transceiver 101 may beprogrammed and functionally tested. In some embodiments, assembledtransceivers 101 may be packaged into their final shipping containersand be ready for sale.

In some embodiments, as illustrated in FIGS. 3 and 4, the antenna 103may be contained within the housing 206 and 220 of the transceiver 101.In some embodiments, the antenna 103 in the transceiver 101 may be smalland/or flat so that the antenna 103 fits within the housing 206 and 220of a small, lightweight transceiver 101. In some embodiments, theantenna 103 may be robust and capable of resisting various impacts. Insome embodiments, the transceiver 101 may be suitable for placement, forexample, on an abdomen area, upper-arm, wrist, or thigh of a patientbody. In some non-limiting embodiments, the transceiver 101 may besuitable for attachment to a patient body by means of a biocompatiblepatch. Although, in some embodiments, the antenna 103 may be containedwithin the housing 206 and 220 of the transceiver 101, this is notrequired, and, in some alternative embodiments, a portion or all of theantenna 103 may be located external to the transceiver housing. Forexample, in some alternative embodiments, antenna 103 may wrap around auser's wrist, arm, leg, or waist such as, for example, the antennadescribed in U.S. Pat. No. 8,073,548, which is incorporated herein byreference in its entirety.

FIG. 5 is a schematic view of an external transceiver 101 according to anon-limiting embodiment. In some embodiments, the transceiver 101 mayhave a connector 902, such as, for example, a Micro-Universal Serial Bus(USB) connector. The connector 902 may enable a wired connection to anexternal device, such as a personal computer (e.g., personal computer109) or a display device 105 (e.g., a smartphone).

The transceiver 101 may exchange data to and from the external devicethrough the connector 902 and/or may receive power through the connector902. The transceiver 101 may include a connector integrated circuit (IC)904, such as, for example, a USB-IC, which may control transmission andreceipt of data through the connector 902. The transceiver 101 may alsoinclude a charger IC 906, which may receive power via the connector 902and charge a battery 908 (e.g., lithium-polymer battery). In someembodiments, the battery 908 may be rechargeable, may have a shortrecharge duration, and/or may have a small size.

In some embodiments, the transceiver 101 may include one or moreconnectors in addition to (or as an alternative to) Micro-USB connector904. For example, in one alternative embodiment, the transceiver 101 mayinclude a spring-based connector (e.g., Pogo pin connector) in additionto (or as an alternative to) Micro-USB connector 904, and thetransceiver 101 may use a connection established via the spring-basedconnector for wired communication to a personal computer (e.g., personalcomputer 109) or a display device 105 (e.g., a smartphone) and/or toreceive power, which may be used, for example, to charge the battery908.

In some embodiments, the transceiver 101 may have a wirelesscommunication IC 910, which enables wireless communication with anexternal device, such as, for example, one or more personal computers(e.g., personal computer 109) or one or more display devices 105 (e.g.,a smartphone). In one non-limiting embodiment, the wirelesscommunication IC 910 may employ one or more wireless communicationstandards to wirelessly transmit data. The wireless communicationstandard employed may be any suitable wireless communication standard,such as an ANT standard, a Bluetooth standard, or a Bluetooth Low Energy(BLE) standard (e.g., BLE 4.0). In some non-limiting embodiments, thewireless communication IC 910 may be configured to wirelessly transmitdata at a frequency greater than 1 gigahertz (e.g., 2.4 or 5 GHz). Insome embodiments, the wireless communication IC 910 may include anantenna (e.g., a Bluetooth antenna). In some non-limiting embodiments,the antenna of the wireless communication IC 910 may be entirelycontained within the housing (e.g., housing 206 and 220) of thetransceiver 101. However, this is not required, and, in alternativeembodiments, all or a portion of the antenna of the wirelesscommunication IC 910 may be external to the transceiver housing.

In some embodiments, the transceiver 101 may include a display interfacedevice, which may enable communication by the transceiver 101 with oneor more display devices 105. In some embodiments, the display interfacedevice may include the antenna of the wireless communication IC 910and/or the connector 902. In some non-limiting embodiments, the displayinterface device may additionally include the wireless communication IC910 and/or the connector IC 904.

In some embodiments, the transceiver 101 may include voltage regulators912 and/or a voltage booster 914. The battery 908 may supply power (viavoltage booster 914) to radio-frequency identification (RFID) reader IC916, which uses the inductive element 103 to convey information (e.g.,commands) to the sensor 101 and receive information (e.g., measurementinformation) from the sensor 100. In some non-limiting embodiments, thesensor 100 and transceiver 101 may communicate using near fieldcommunication (NFC) (e.g., at a frequency of 13.56 MHz). In theillustrated embodiment, the inductive element 103 is a flat antenna. Insome non-limiting embodiments, the antenna may be flexible. However, asnoted above, the inductive element 103 of the transceiver 101 may be inany configuration that permits adequate field strength to be achievedwhen brought within adequate physical proximity to the inductive element114 of the sensor 100. In some embodiments, the transceiver 101 mayinclude a power amplifier 918 to amplify the signal to be conveyed bythe inductive element 103 to the sensor 100.

The transceiver 101 may include a peripheral interface controller (PIC)microcontroller 920 and a memory 922 (e.g., Flash memory), which may benon-volatile and/or capable of being electronically erased and/orrewritten. The PIC microcontroller 920 may control the overall operationof the transceiver 101. For example, the PIC microcontroller 920 maycontrol the connector IC 904 or wireless communication IC 910 totransmit data via wired or wireless communication and/or control theRFID reader IC 916 to convey data via the inductive element 103. The PICmicrocontroller 920 may also control processing of data received via theinductive element 103, connector 902, or wireless communication IC 910.

In some embodiments, the transceiver 101 may include a sensor interfacedevice, which may enable communication by the transceiver 101 with asensor 100. In some embodiments, the sensor interface device may includethe inductive element 103. In some non-limiting embodiments, the sensorinterface device may additionally include the RFID reader IC 916 and/orthe power amplifier 918. However, in some alternative embodiments wherethere exists a wired connection between the sensor 100 and thetransceiver 101 (e.g., transcutaneous embodiments), the sensor interfacedevice may include the wired connection.

In some embodiments, the transceiver 101 may include a display 924(e.g., liquid crystal display and/or one or more light emitting diodes),which PIC microcontroller 920 may control to display data (e.g., analytelevels values). In some embodiments, the transceiver 101 may include aspeaker 926 (e.g., a beeper) and/or vibration motor 928, which may beactivated, for example, in the event that an alarm condition (e.g.,detection of a hypoglycemic or hyperglycemic condition) is met. Thetransceiver 101 may also include one or more additional sensors 930,which may include an accelerometer and/or temperature sensor, which maybe used in the processing performed by the PIC microcontroller 920.

In some embodiments, the transceiver 101 may be a body-worn transceiverthat is a rechargeable, external device worn over the sensorimplantation or insertion site. The transceiver 101 may supply power tothe proximate sensor 100, calculate analyte levels from data receivedfrom the sensor 100, and/or transmit the calculated analyte levels to adisplay device 105 (see FIG. 1). Power may be supplied to the sensor 100through an inductive link (e.g., an inductive link of 13.56 MHz). Insome embodiments, the transceiver 101 may be placed using an adhesivepatch or a specially designed strap or belt. The external transceiver101 may read measured analyte data from a subcutaneous sensor 100 (e.g.,up to a depth of 2 cm or more). The transceiver 101 may periodically(e.g., every 2, 5, or 10 minutes) read sensor data and calculate ananalyte level and an analyte level trend. From this information, thetransceiver 101 may also determine if an alert and/or alarm conditionexists, which may be signaled to the user (e.g., through vibration byvibration motor 928 and/or an LED of the transceiver's display 924and/or a display of a display device 105).

The information from the transceiver 101 (e.g., calculated analytelevels, calculated analyte level trends, alerts, alarms, and/ornotifications) may be transmitted to a display device 105 (e.g., viaBluetooth Low Energy with Advanced Encryption Standard (AES)-CounterCBC-MAC (CCM) encryption) for display by a mobile medical application(MMA) being executed by the display device 105. In some non-limitingembodiments, the MMA may provide alarms, alerts, and/or notifications inaddition to any alerts, alarms, and/or notifications received from thetransceiver 101. In one embodiment, the MMA may be configured to providepush notifications. In some embodiments, the transceiver 101 may have apower button (e.g., button 208) to allow the user to turn the device onor off, reset the device, or check the remaining battery life. In someembodiments, the transceiver 101 may have a button, which may be thesame button as a power button or an additional button, to suppress oneor more user notification signals (e.g., vibration, visual, and/oraudible) of the transceiver 101 generated by the transceiver 101 inresponse to detection of an alert or alarm condition.

In some embodiments, the transceiver 101 of the analyte monitoringsystem 50 may receive raw signals indicative of an amount orconcentration of an analyte in the interstitial fluid (“ISF”) inproximity to the analyte indicator element 106 of the analyte sensor100. In some embodiments, the transceiver 101 may receive the rawsignals from the sensor 100 periodically (e.g., every 1, 2, 5, 10, 15,or 20 minutes). In some embodiments, the raw signals may include one ormore measurements (e.g., one or more measurements indicative of thelevel of emission light 331 from the indicator molecules 104 as measuredby the photodetector 224, one or more measurements indicative of thelevel of reference light 333 as measured by photodetector 226, and/orone or more temperature measurements as measured by the temperaturetransducer 670). In some embodiments, the transceiver 101 may use thereceived raw signals to calculate an ISF analyte level.

In some embodiments, the transceiver 101 may use the calculated ISFanalyte level and one or more previously calculated ISF analyte levelsto calculate a rate of change of the interstitial fluid analyte level(“ISF_ROC”). In some non-limiting embodiments, to calculate ISF_ROC, thetransceiver 101 may use just the calculated ISF analyte level and themost recent previously calculated ISF analyte level and determineISF_ROC as the difference between the calculated ISF analyte level andmost recent previously calculated ISF analyte level divided by the timedifference between a time stamp for the calculated ISF analyte level anda time stamp for the most recent previously calculated ISF analytelevel. In some alternative embodiments, to calculate ISF_ROC, thetransceiver 101 may use the calculated ISF analyte level and a pluralityof the most recent previously calculated ISF analyte levels. In somenon-limiting embodiments, the plurality of the most recent previouslycalculated ISF analyte levels may be, for example and withoutlimitation, the previous two calculated ISF analyte levels, the previous20 calculated ISF analyte levels, or any number of previously calculatedISF analyte levels in between (e.g., the previous 5 calculated analytelevels). In other alternative embodiments, to calculate ISF_ROC, thetransceiver 101 may use the calculated ISF analyte level and thepreviously calculated ISF analyte levels that were calculated during atime period. In some non-limiting embodiments, the time period may be,for example and without limitation, the last one minute, the last 60minutes, or any amount of time in between (e.g., the last 25 minutes).In some embodiments where the transceiver 101 uses the calculated ISFanalyte level and more than one previously calculated ISF analyte levelsto calculate ISF_ROC, the transceiver 101 may use, for example, linearor non-linear regression to calculate ISF_ROC.

In some embodiments, the transceiver 101 may convert the calculated ISFanalyte level into a blood analyte level by performing a lagcompensation, which compensates for the lag between blood analyte leveland an ISF analyte level. In some embodiments, the transceiver 101 maycalculate the blood analyte level using at least the calculated ISFanalyte level and the calculated ISF_ROC. In some non-limitingembodiments, the transceiver 101 may calculate the blood analyte levelas ISF_ROC/p₂+(1+p₃/p₂)*ISF_analyte, where p₂ is an analyte diffusionrate, p₃ is an analyte consumption rate, and ISF_analyte is thecalculated ISF analyte level.

In some embodiments, the transceiver 101 may store one or more of thecalculated ISF analyte level, calculated ISF_ROC, and calculated bloodanalyte level (e.g., in memory 922). In some embodiments, thetransceiver 101 may convey the calculated blood analyte level to thedisplay device 105, and the display device 105 may display thecalculated blood analyte level.

In some embodiments, the transceiver 100 may store one or more of thecalculated ISF analyte level, calculated ISF_ROC, and calculated bloodanalyte level (e.g., in memory 922). In some embodiments, thetransceiver 100 may convey the calculated blood analyte level to thedisplay device 105, and the display device 105 may display thecalculated blood analyte level.

FIG. 6 is a block diagram of a non-limiting embodiment of the displaydevice 105 of the analyte monitoring system 50. As shown in FIG. 6, insome embodiments, the display device 105 may include one or more of aconnector 602, a connector integrated circuit (IC) 604, a charger IC606, a battery 608, a computer 610, a first wireless communication IC612, a memory 614, a second wireless communication IC 616, and a userinterface 640.

In some embodiments in which the display device 105 includes theconnector 602, the connector 602 may be, for example and withoutlimitation, a Micro-Universal Serial Bus (USB) connector. The connector602 may enable a wired connection to an external device, such as apersonal computer or transceiver 101 (e.g., via the connector 902 of thetransceiver 101). The display device 105 may exchange data to and fromthe external device through the connector 602 and/or may receive powerthrough the connector 602. In some embodiments, the connector IC 604 maybe, for example and without limitation, a USB-IC, which may controltransmission and receipt of data through the connector 602.

In some embodiments in which the display device 105 includes the chargerIC 606, the charger IC 606 may receive power via the connector 602 andcharge the battery 608. In some non-limiting embodiments, the battery608 may be, for example and without limitation, a lithium-polymerbattery. In some embodiments, the battery 608 may be rechargeable, mayhave a short recharge duration, and/or may have a small size.

In some embodiments, the display device 105 may include one or moreconnectors and/or one or more connector ICs in addition to (or as analternative to) connector 602 and connector IC 604. For example, in somealternative embodiments, the display device 105 may include aspring-based connector (e.g., Pogo pin connector) in addition to (or asan alternative to) connector 602, and the display device 105 may use aconnection established via the spring-based connector for wiredcommunication to a personal computer or the transceiver 101 and/or toreceive power, which may be used, for example, to charge the battery608.

In some embodiments in which the display device 105 includes the firstwireless communication IC 612, the first wireless communication IC 612may enable wireless communication with one or more external devices,such as, for example, one or more personal computers, one or moretransceivers 101, one or more other display devices 105, and/or one ormore devices 109 (e.g., one or more wearable devices). In somenon-limiting embodiments, the first wireless communication IC 612 mayemploy one or more wireless communication standards to wirelesslytransmit data. The wireless communication standard employed may be anysuitable wireless communication standard, such as an ANT standard, aBluetooth standard, or a Bluetooth Low Energy (BLE) standard (e.g., BLE4.0). In some non-limiting embodiments, the first wireless communicationIC 612 may be configured to wirelessly transmit data at a frequencygreater than 1 gigahertz (e.g., 2.4 or 5 GHz). In some embodiments, thefirst wireless communication IC 612 may include an antenna (e.g., aBluetooth antenna). In some non-limiting embodiments, the antenna of thefirst wireless communication IC 612 may be entirely contained within ahousing of the display device 105. However, this is not required, and,in alternative embodiments, all or a portion of the antenna of the firstwireless communication IC 612 may be external to the display devicehousing.

In some embodiments, the display device 105 may include a transceiverinterface, which may enable communication by the display device 105 withone or more transceivers 101. In some embodiments, the transceiverinterface may include the antenna of the first wireless communication IC612 and/or the connector 602. In some non-limiting embodiments, thetransceiver interface may additionally or alternatively include thefirst wireless communication IC 612 and/or the connector IC 604.

In some embodiments in which the display device 105 includes the secondwireless communication IC 616, the second wireless communication IC 616may enable the display device 105 to communicate with a remote datamanagement system (DMS) and/or one or more remote devices (e.g.,smartphones, servers, and/or personal computers) via wireless local areanetworks (e.g., Wi-Fi), cellular networks, and/or the Internet. In somenon-limiting embodiments, the second wireless communication IC 616 mayemploy one or more wireless communication standards to wirelesslytransmit data. In some embodiments, the second wireless communication IC616 may include one or more antennas (e.g., a Wi-Fi antenna and/or oneor more cellular antennas). In some non-limiting embodiments, the one ormore antennas of the second wireless communication IC 616 may beentirely contained within a housing of the display device 105. However,this is not required, and, in alternative embodiments, all or a portionof the one or more antennas of the second wireless communication IC 616may be external to the display device housing.

In some embodiments in which the display device 105 includes the memory614, the memory 614 may be non-volatile and/or capable of beingelectronically erased and/or rewritten. In some embodiments, the memory614 may be, for example and without limitations a Flash memory.

In some embodiments in which the display device 105 includes thecomputer 610, the computer 610 may control the overall operation of thedisplay device 105. For example, the computer 610 may control theconnector IC 604, the first wireless communication IC 612, and/or thesecond wireless communication IC 616 to transmit data via wired orwireless communication. The computer 610 may additionally oralternatively control processing of received data (e.g., analytemonitoring data received from the transceiver 101).

In some embodiments in which the display device 105 includes the userinterface 640, the user interface 640 may include one or more of adisplay 620 and a user input 622. In some embodiments, the display 620may be a liquid crystal display (LCD) and/or light emitting diode (LED)display. In some non-limiting embodiments, the user input 622 mayinclude one or more buttons, a keyboard, a keypad, and/or a touchscreen.In some embodiments, the computer 610 may control the display 620 todisplay data (e.g., analyte levels, analyte level rate of changeinformation, alerts, alarms, and/or notifications). In some embodiments,the user interface 640 may include one or more of a speaker 624 (e.g., abeeper) and a vibration motor 626, which may be activated, for example,in the event that a condition (e.g., a hypoglycemic or hyperglycemiccondition) is met.

In some embodiments, the computer 610 may execute a mobile medicalapplication (MMA). In some embodiments, the display device 105 mayreceive analyte monitoring data from the transceiver 101. In somenon-limiting embodiments, the received analyte monitoring data mayinclude one or more analyte levels, one or more analyte level rates ofchange, and/or one or more sensor measurements. In some embodiments, thereceived analyte monitoring data may additionally or alternativelyinclude alarms, alerts, and/or notifications. In some embodiments, theMMA may display some or all of the received analyte monitoring data onthe display 620 of the display device 105. In some alternativeembodiments, the received analyte monitoring data may include one ormore sensor measurements and does not include analyte levels, and thedisplay device 105 may calculate one or more analyte levels using theone or more sensors measurements. In some alternative embodiments, thereceived analyte monitoring data may include one or more analyte levelsbut does not include analyte level rates of change, and the displaydevice 105 may calculate one or more analyte level rates of change usingthe one or more analyte levels. In some non-limiting alternativeembodiments, the display device 105 may calculate one or more analytelevels and calculate one or more analyte level rates of change using atleast the one or more analyte levels calculated by the display device105.

In some embodiments, the analyte monitoring system 50 may calibrate theconversion of raw signals to blood analyte levels. In some embodiments,the calibration may be performed approximately periodically (e.g.,approximately every 12 or 24 hours). In some embodiments, thecalibration may be performed using one or more reference measurements(e.g., one or more self-monitoring blood glucose (SMBG) measurements).In some non-limiting embodiments, the display device 105 may prompt auser for one or more reference measurements using, for example andwithout limitation the user interface 640 (e.g., the display 620,speaker 624, and/or vibration motor 626 of the user interface 640) ofthe display device 105. In some embodiments, the one or more referencemeasurements may be entered into the analyte monitoring system 50 usingthe user interface 640 (e.g., the user input 622 of the user interface640) of the display device 105. In some embodiments, the display device105 may convey one or more references measurements to the transceiver101 (e.g., using the first wireless communication IC 612 and/or theconnector 602). In some embodiments, the transceiver 101 may receive theone or more reference measurements from the display device 105 and usethe one or more reference measurements to perform the calibration. Inresponse, the user may enter the one or more reference measurements intothe display device 105 using, for example and without limitation, theuser interface 640 (e.g., the user input 622 of the user interface 640)of the display device 105.

FIG. 7 is a block diagram of a non-limiting embodiment of the computer610 of the analyte monitoring system 50. As shown in FIG. 7, in someembodiments, the computer 610 may include one or more processors 522(e.g., a general purpose microprocessor) and/or one or more circuits,such as an application specific integrated circuit (ASIC),field-programmable gate arrays (FPGAs), a logic circuit, and the like.In some embodiments, the computer 610 may include a data storage system(DSS) 523. The DSS 523 may include one or more non-volatile storagedevices and/or one or more volatile storage devices (e.g., random accessmemory (RAM)). In embodiments where the computer 610 includes aprocessor 522, the DSS 523 may include a computer program product (CPP)524. CPP 524 may include or be a computer readable medium (CRM) 526. TheCRM 526 may store a computer program (CP) 528 comprising computerreadable instructions (CRI) 530. In some embodiments, the CRM 526 maystore, among other programs, the MMA, and the CRI 530 may include one ormore instructions of the MMA. The CRM 526 may be a non-transitorycomputer readable medium, such as, but not limited, to magnetic media(e.g., a hard disk), optical media (e.g., a DVD), solid state devices(e.g., random access memory (RAM) or flash memory), and the like. Insome embodiments, the CRI 530 of computer program 528 may be configuredsuch that when executed by processor 522, the CRI 530 causes thecomputer 610 to perform steps described below (e.g., steps describedbelow with reference to the MMA). In other embodiments, the computer 610may be configured to perform steps described herein without the need fora computer program. That is, for example, the computer 610 may consistmerely of one or more ASICs. Hence, the features of the embodimentsdescribed herein may be implemented in hardware and/or software.

In some embodiments in which the user interface 640 of the displaydevice 105 includes the display 618, the MMA may cause the displaydevice 105 to provide a series of graphical control elements or widgetsin the user interface 640, such as a graphical user interface (GUI),shown on the display 618. The MMA may, for example without limitation,cause the display device 105 to display analyte related information in aGUI such as, but not limited to: one or more of analyte information,current analyte levels, past analyte levels, predicted analyte levels,user notifications, analyte status alerts and alarms, trend graphs,analyte level rate of change or trend arrows, and user-entered events.In some embodiments, the MMA may provide one or more graphical controlelements that may allow a user to manipulate aspects of the one or moredisplay screens. Although aspects of the MMA are illustrated anddescribed in the context of glucose monitoring system embodiments, thisis not required, and, in some alternative embodiments, the MMA may beemployed in other types of analyte monitoring systems.

In some embodiments where the display device 105 communicates with atransceiver 101, which in turn obtains sensor measurement data from theanalyte sensor 100, the MMA may cause the display device 105 to receiveand display one or more of analyte data, trends, graphs, alarms, andalerts from the transceiver 101. In some embodiments, the MMA may storeanalyte level history and statistics for a patient on the display device105 (e.g., in memory 614 and/or DSS 533) and/or in a remote data storagesystem.

In some embodiments, a user of the display device 105, which may be thesame or different individual as patient, may initiate the download ofthe MMA from a central repository over a wireless cellular network orpacket-switched network, such as the Internet. Different versions of theMMA may be provided to work with different commercial operating systems,such as the Android OS or Apple OS running on commercial smart phones,tablets, and the like. For example, where display device 105 is an AppleiPhone, the user may cause the display device 105 to access the AppleiTunes store to download a MMA compatible with an Apple OS, whereaswhere the display device 105 is an Android mobile device, the user maycause the display device 105 to access the Android App Store to downloada MMA compatible with an Android OS.

FIG. 8 is a flow chart illustrating a process 800 for controllinginitialization and calibration of an analyte monitoring system 50. Insome embodiments, the transceiver 101 performs one or more steps of thecontrol process 800. In some non-limiting embodiments, the PICmicrocontroller 920 of the transceiver 101 performs one or more steps ofthe control process 800. In some embodiments, the process 800 may beginafter insertion or implantation of the analyte sensor 100.

In some embodiments, the process 800 may begin with a warm up phase 802in which the transceiver 101 allows the sensor 100 to adjust to beingfully or partially in the body. In some non-limiting embodiments, thewarm up phase 802 may give the analyte indicator element 106 time tohydrate. In some non-limiting embodiments, the transceiver 101 stays inthe warm up phase 802 for a predetermined period of time such as, forexample and without limitation, 12 or 24 hours. However, this is notrequired, and, in some alternative embodiments, the transceiver 101 maymonitor sensor conditions during the warm up phase 802 and exit the warmup phase 802 after the sensor conditions have stabilized. In someembodiments, after completion of the warm up phase 802, the process 800may proceed to an initialization phase 804. In some alternativeembodiments, the warm up phase 802 may not be necessary (e.g., when theanalyte sensor 100 is an external sensor or does not need time toacclimate to being inside the body). In these alternative embodiments,the process 800 may begin in an initialization step 804.

In some embodiments, in the initialization phase 804, the transceiver101 may receive sensor data. In some non-limiting embodiments, thetransceiver 101 may receive the sensor data periodically (e.g., every 1,2, 5, 10, 15, or 20 minutes). In some embodiments, in the initializationphase 804, the transceiver 101 may receive one or more referencemeasurements. In some non-limiting embodiments, the transceiver 101 mayreceive three or more reference measurements in the initialization phase804. In some non-limiting embodiments, the transceiver 101 may receivethe reference measurements periodically (e.g., approximately every 6hours). In some embodiments, the transceiver 101 may store the referencemeasurements in a calibration point memory, which may be, for exampleand without limitation, a circular buffer. In some embodiments, thetransceiver 101 may use the one or more reference measurements ascalibration points to perform an initial calibration of the conversionfunction used to calculate blood analyte measurements from the sensordata. In some embodiments, the transceiver 101 may receive the one ormore reference measurements from the user interface of the displaydevice 105. In some non-limiting embodiments, the transceiver 101 maycause the display device 105 to prompt a user for the one or morereference measurements using, for example and without limitation theuser interface 640 (e.g., the display 620, speaker 624, and/or vibrationmotor 626 of the user interface 640) of the display device 105. Inresponse, the user may enter the one or more reference measurements intothe display device 105 using, for example and without limitation, theuser interface 640 (e.g., the user input 622 of the user interface 640)of the display device 105.

In some non-limiting embodiments, during the initialization phase 804,no analyte measurements are displayed to the user. In some embodiments,after the completion of the initialization phase 804, the process 800may proceed to a calibration phase 806. In some embodiments, thecalibration phase 806 may be a steady state phase.

In some embodiments, in the calibration phase 806, the transceiver 101may receive sensor data and calculate blood analyte measurements usingthe conversion function and the received sensor data. In somenon-limiting embodiments, the transceiver 101 may receive the sensordata periodically (e.g., every 1, 2, 5, 10, 15, or 20 minutes). In someembodiments, the transceiver 101 may display one or more blood analytemeasurements. In some non-limiting embodiments, in the calibration phase806, the transceiver 101 may display the one or more blood analytemeasurements by transmitting them to the display device 105 for display.

In some embodiments, in the calibration phase 806, the transceiver 101may receive one or more reference measurements. In some non-limitingembodiments, the transceiver 101 may receive the reference measurementsperiodically (e.g., approximately every 12 hours). In some non-limitingembodiments, the transceiver 101 may receive the reference measurementsless frequently than in the initialization phase 804. However, this isnot required. It is also not required that the transceiver 101 receivereference measurements periodically, and, in some alternativeembodiments, the transceiver 101 may receive reference measurements onan as-needed basis (e.g., as determined by the transceiver 101 byanalyzing the sensor data). In some embodiments, the transceiver 101 mayreceive the reference measurements from the display device 105. In somenon-limiting embodiments, in the calibration phase 806, the transceiver101 may cause the display device 105 to prompt a user for the one ormore reference measurements using, for example and without limitationthe user interface 640 of the display device 105. In response, the usermay enter the one or more reference measurements into the display device105 using, for example and without limitation, the user interface 640 ofthe display device 105.

In some embodiments, in the sensor dropout phase 808, the transceiver101 may receive sensor data from the sensor 100, but no analytemeasurements are displayed to the user. In some embodiments, the process800 may remain in the dropout phase 808 for a period of time (e.g., atleast six hours) before proceeding back to the initialization phase 804.However, the sensor dropout phase 808 is not necessary, and, in somealternative embodiments, the process 800 may proceed directly to theinitialization phase 804 from the calibration phase 806.

FIG. 9 is a flow chart illustrating a calibration process 700, which maybe performed during the calibration phase 806 of the control process 800illustrated in FIG. 8. In some embodiments, the transceiver 101 mayperform one or more steps of the calibration process 700. In somenon-limiting embodiments, the PIC microcontroller 920 of the transceiver101 may perform one or more steps of the calibration process 700.

In some embodiments, as shown in FIG. 9, the calibration process 700 mayinclude a step 702 in which the transceiver 101 determines whether thetransceiver 101 has received sensor data (e.g., light and/or temperaturemeasurements) from the sensor 100. In some embodiments, the sensor datamay be received following a command (e.g., a measurement command or aread sensor data command) conveyed from the transceiver 101 to thesensor 100. However, this is not required, and, in some alternativeembodiments, the sensor 100 may control when sensor data is conveyed tothe transceiver 101, or the sensor 100 may continuously convey sensordata to the transceiver 101. In some non-limiting embodiments, thetransceiver 101 may receive the sensor data periodically (e.g., every 1,2, 5, 10, 15, or 20 minutes). In some embodiments, the transceiver 101may receive the sensor data wirelessly. For example and withoutlimitation, in some non-limiting embodiments, the transceiver 101 mayreceive the sensor data by detecting modulations in an electromagneticwave generated by the sensor 100 (e.g., by detecting modulations in thecurrent flowing through the coil 103 of the transceiver 101). However,this is not required, and, in some alternative embodiments, thetransceiver 101 may receive the sensor data via a wired connection tothe sensor 100. In some non-limiting embodiments, if the sensor hasreceived sensor data, the calibration process 700 may proceed from step702 to a measurement calculation step 704. In some non-limitingembodiments, if the transceiver 101 has not received sensor data, thecalibration process 700 may proceed from step 702 to a step 706.

In some non-limiting embodiments, the calibration process 700 mayinclude the measurement calculation step 704. In some embodiments, thestep 704 may include calculating a sensor measurement SM1 using thecurrent conversion function and the received sensor data. In someembodiments, the sensor measurement SM1 may be a measurement of a bloodanalyte level. In some embodiments, the measurement calculation step 704may include calculating an ISF analyte level, an ISF_ROC, and the bloodanalyte level.

In some non-limiting embodiments, in the measurement calculation step704, the transceiver 101 may calculate the ISF analyte level using thereceived sensor data. In some embodiments, the ISF analyte level may bea measurement of the amount or concentration of the analyte in theinterstitial fluid in proximity to the analyte indicator element 106. Insome non-limiting embodiments, calculation of the ISF analyte level mayinclude, for example and without limitation, some or all of the featuresdescribed in U.S. application Ser. No. 13/937,871, filed on Jul. 9,2013, which is incorporated by reference herein in its entirety.

In some non-limiting embodiments, in the measurement calculation step704, the transceiver 101 may calculate the ISF_ROC using at least thecalculated ISF analyte level. In some non-limiting embodiments, thetransceiver 101 may calculate the ISF_ROC using at least the calculatedISF analyte level and one or more previously calculated ISF analytelevels (e.g., one or more ISF analyte levels calculated using previouslyreceived sensor data).

In some non-limiting embodiments, in the measurement calculation step704, the transceiver 101 may calculate the blood analyte level byperforming a lag compensation. In some embodiments, the transceiver 101may calculate the blood analyte level using at least the calculated ISFanalyte level and the calculated ISF_ROC. In some non-limitingembodiments, the transceiver 101 may calculate the blood analyte levelusing the formula ISF_ROC/p₂+(1+p₃/p₂)*ISF_analyte, where p₂ is theanalyte diffusion rate, p₃ is the analyte consumption rate, ISF_ROC isthe calculated ISF_ROC, and ISF_analyte is the calculated ISF analytelevel. However, this is not required, and some alternative embodimentsmay use a different formula for calculating the blood analyte level.

For example, in some non-limiting alternative embodiments, thetransceiver 101 may calculate the sensor measurement SM1 by utilizing atwo-compartment model, such as, for example:

$\frac{{dC}_{2}}{dt} = {{p_{2}*\left\lbrack {{C_{1}(t)} - {C_{2}(t)}} \right\rbrack} - {p_{3}*{C_{2}(t)}}}$

In some embodiments, C₂ may represent the ISF analyte level. In someembodiments, C₁ may represent the sensor measurement SM1, which may be ablood analyte level. In some embodiments, p₂ and p₃ may represent ananalyte diffusion rate and an analyte consumption rate, respectively, asthe analyte diffuses from the ISF to the blood.

In some embodiments, the transceiver 101 may solve for the concentrationof analyte in blood (C₁) according to the following two-compartmentmodel, wherein the variables retain the same definition as describedabove:

${C_{1}(t)} = {{\frac{1}{p_{2}}\frac{{dC}_{2}}{dt}} + {\left( {1 + \frac{p_{3}}{p_{2}}} \right)*{C_{2}(t)}}}$

In some non-limiting embodiments, the lag parameters may be one or moreof 1/p₂ and p₃/p₂. In some non-limiting parameters, the lag parametersmay be one or more of p₂ and p₃.

In some non-limiting embodiments, the transceiver 101 may employ anasymmetrical lag methodology when converting an ISF analyte level into ablood analyte level. In some embodiments, the asymmetrical lagmethodology may reflect physiological analyte level changes moreaccurately than a symmetrical lag methodology. In some non-limitingembodiments, the asymmetrical lag methodology may more reflectphysiological glucose level changes during a hypoglycemic state moreaccurately than a symmetrical lag methodology. In some non-limitingembodiments, the asymmetrical lag methodology may be designed to moreclosely mimic the normal physiological response to (and protectionagainst) the hypoglycemic state. In some non-limiting embodiments, theasymmetrical lag methodology may include one or more of: (i)decelerating the rate of change in further falling glucose levels inhypoglycemia and (ii) accelerating glucose rises when recovering from ahypoglycemic or low blood glucose event.

In some non-limiting embodiments in which the asymmetrical lagmethodology decelerates the falling rate of change, the asymmetrical lagmethodology may include determining whether the calculated ISF analytelevel is less than or equal to a low ISF analyte level threshold (e.g.,a hypoglycemia ISF threshold). In some non-limiting embodiments, the lowISF analyte level threshold may be, for example and without limitation,70 mg/dL, but other values may be used in alternative embodiments. Insome non-limiting embodiments, the asymmetrical lag methodology mayinclude determining whether the calculated ISF_ROC is less than a lowanalyte level ISF_ROC lower limit threshold (e.g., a hypoglycemiaISF_ROC lower limit threshold). In some non-limiting embodiments, thelow analyte level ISF_ROC lower limit threshold may be, for example andwithout limitation, −1.3 mg/dL/min, but other values may be used inalternative embodiments. In some non-limiting embodiments, if thecalculated ISF analyte level is less than or equal to the low ISFanalyte level threshold and the calculated ISF_ROC is less than a lowanalyte level ISF_ROC lower limit threshold, the asymmetrical lagmethodology may include using the low analyte level ISF_ROC lower limitthreshold instead of the calculated ISF_ROC to calculate the bloodanalyte level.

In some non-limiting embodiments in which the asymmetrical lagmethodology decelerates the falling rate of change, the asymmetrical lagmethodology may additionally or alternatively include determiningwhether the calculated blood analyte level is less than a low analytelevel linear fit threshold (e.g., a hypoglycemia linear fit threshold).In some non-limiting embodiments, the low analyte level linear fitthreshold may be lower than the low ISF analyte level threshold. In somenon-limiting embodiments, the low analyte level linear fit threshold maybe, for example and without limitation, 50 mg/dL, but other values maybe used in alternative embodiments. In some non-limiting embodiments, ifthe calculated blood analyte level is less than the low analyte levellinear fit threshold, the asymmetrical lag methodology may adjust thecalculated blood analyte level using the following linear equation:adjusted BG=BG*LinearFit_slope+LinearFit_intercept, wherein the adjustedBG is the adjusted blood analyte level, and BG is the calculated bloodanalyte level. In some non-limiting embodiments, the LinearFit_slope andLinearFit_intercept may be determined using experimental data.

In some non-limiting embodiments, the asymmetrical lag methodology mayinclude determining whether the calculated blood analyte level (or theadjusted blood analyte level if the calculated blood analyte level hasbeen adjusted using the linear equation) is less than a low bloodanalyte level threshold (e.g., a hypoglycemia blood threshold). In somenon-limiting embodiments, the low blood analyte level threshold may be,for example and without limitation, 70 mg/dL, but other values may beused in alternative embodiments. In some non-limiting embodiments, theasymmetrical lag methodology may include calculating an instantaneousblood analyte level rate of change (e.g., using the current bloodanalyte and one or more previous blood analyte levels). In somenon-limiting embodiments, the asymmetrical lag methodology may includedetermining whether the calculated instantaneous blood analyte levelrate of change is less than a low blood analyte level rate of changethreshold (e.g., a hypoglycemia blood analyte level rate of changethreshold). In some non-limiting embodiments, the low blood analytelevel rate of change threshold may be, for example and withoutlimitation, −1.2 mg/dL/min, but other values may be used in alternativeembodiments. In some non-limiting embodiments, if the calculated bloodanalyte level is less than the low blood analyte level and thecalculated instantaneous blood analyte level rate of change is less thanthe low blood analyte level rate of change threshold, the asymmetricallag methodology may update the current blood analyte level as follows:BG(n)=BG(n−1)+Low_BG_ROC_Limit*dTime, where BG(n) is the currentcalculated blood analyte, BG(n−1) is the previous calculated bloodanalyte level, Low_BG_ROC_Limit is the low blood analyte level rate ofchange threshold, and dTime is the number of minutes between the currentand the previous sensor measurements.

In some non-limiting embodiments in which the asymmetrical lagmethodology accelerates glucose rises during recovery from ahypoglycemic or low blood glucose event, the asymmetrical lagmethodology may include determining whether the calculated ISF analytelevel is less than or equal to an adjust diffusion time threshold. Insome non-limiting embodiments, the asymmetrical lag methodology mayinclude determining whether the ISF analyte level is rising. In somenon-limiting embodiments, if the calculated ISF analyte level is lessthan or equal to an adjust diffusion time threshold and rising, theasymmetrical lag methodology may include multiplying a lag parameterassociated with diffusion time (e.g., 1/p₂) by a factor [e.g., 1.1], andusing the adjusted lag parameter in the conversion function to calculatethe blood analyte level. In some non-limiting embodiments, the factormay be, for example and without limitation, 1.1, but other factors maybe used in alternative embodiments.

In some embodiments, in step 704, the transceiver 101 may display thecalculated sensor measurement SM1. In some non-limiting embodiments, thetransceiver 101 may display the sensor measurement SM1 by transmittingit to the display device 105 for display.

In some non-limiting embodiments, the calibration process 700 mayinclude the step 706 in which the transceiver 101 determines whether thetransceiver 101 has received a reference measurement RM1. The referencemeasurement RM1 may be, for example and without limitation, an SMBGmeasurement obtained from, for example and without limitation, afinger-stick blood sample. In some embodiments, the transceiver 101 mayreceive reference measurements periodically or on an as-needed basis. Insome embodiments, the transceiver 101 may receive the referencemeasurement RM1 from the display device 105. In some non-limitingembodiments, the transceiver 101 may cause the display device 105 toprompt a user for the reference measurement RM1, and, in response, theuser may enter the reference measurement RM1 into the display device105. In some alternative embodiments, the transceiver 101 may prompt auser for the reference measurement RM1, and, in response, the user mayenter the reference measurement RM1 directly into the transceiver 101.

In some embodiments, the transceiver 101 may receive the referencemeasurement RM1 with a reference time stamp. In some embodiments, thedevice into which the reference measurement RM1 is entered by a user(e.g., the display device 105 or the transceiver 101) may assign thereference time stamp to the reference measurement RM1 when the userenters the reference measurement RM1 into the device, and the referencetime stamp may indicate the time at which the user entered the referencemeasurement RM1 into the device. However, this is not required, and, insome alternative embodiments, the reference time stamp may be a timeentered by a user to indicate a time at which the reference measurementwas taken (e.g., a time at which blood was drawn for an SMBGmeasurement). In some non-limiting alternative embodiments, a user mayenter a time at which a reference measurement was taken before, at thesame time as, or after the user enters a reference measurement RM1. Inone non-limiting alternative embodiment, the device into which the userenters the reference measurement RM1 (e.g., the display device 105 orthe transceiver 101) may prompt the user to enter a time at which thereference measurement was taken. In some non-limiting embodiments, thedevice that prompts the user for the reference measurement RM1 (e.g.,the display device 105 or the transceiver 101) may additionally promptthe user to enter a time at which the reference measurement was taken.In some other alternative embodiments, transceiver 101 may assign thereference time stamp to the reference measurement RM1 when thetransceiver 101 receives the reference measurement RM1 from the displaydevice 105, and the reference time stamp may indicate the time at whichthe transceiver 101 receives the reference measurement RM1 from thedisplay device 105.

In some embodiments, if the transceiver 101 has not received a referencemeasurement RM1, the calibration process 700 may proceed to a step 712.In some embodiments, if the transceiver 101 has received a referencemeasurement RM1, the calibration process 700 may proceed to a step 708.

In some non-limiting embodiments, the calibration process 700 mayinclude the step 712 in which the transceiver 101 determines whether toupdate one or more lag parameters (e.g., one or more of 1/p₂ and p₃/p₂or one or more of the analyte diffusion rate p₂ and the analyteconsumption rate p₃). In some embodiments, the decision of whether toupdate the parameters of the transport model will be made according to,for example and without limitation, whether a length of time has passedsince the parameters were last updated. For example and withoutlimitation, in one non-limiting embodiment, the transceiver 101 mayupdate one or more of the lag parameters periodically (e.g., every 1, 2,5, 10, 20, or 30 days). In some alterative embodiments, the life of theanalyte sensor 100 after insertion may be divided into a number of timeperiods (e.g., 2, 3, 4, 5, 6, 7, 8, 10, 15, 20, 50, or 100 timeperiods), and the decision of whether to update the parameters of thetransport model will be made according to whether the life of theanalyte sensor 100 has passed into a new time period, and different lagparameters may be associated with the different time periods. Forexample and without limitation, in one non-limiting alternativeembodiment, the life of the analyte sensor 100 after insertion may bedivided into the following six periods: (1) Day 0 to Day 5, (2) Day 5 toDay 10, (3) Day 10 to Day 20, (4) Day 20 to Day 45, (5) Day 45 to Day75, and (6) greater than Day 75, and different lag parameters may beassociated with the six periods.

If the transceiver 101 determines that one or more of the lag parametersshould be updated, the calibration process 700 may proceed to a lagparameter updating step 714 in which the transceiver 101 may update oneor more of the lag parameters. In some embodiments, lag parametersassociated with the different time periods may be stored in a memory ofthe transceiver 101 (e.g., memory 922). In some non-limitingembodiments, the memory may store different values for one or more of1/p₂ and p₃/p₂. For example and without limitation, in one non-limitingembodiment, the memory may store the following values for 1/p₂: 1689 forthe Day 0 to Day 5 period and for the Day 5 to Day 10 period, 1478 forthe Day 10 to Day 20 period, and 1230 for the Day 20 to Day 45 periodand for the greater than Day 75 period. For example and withoutlimitation, in one non-limiting embodiment, the memory may store thefollowing values for p₃/p₂: 0.1551 for the Day 0 to Day 5 period and forthe Day 5 to Day 10 period, 0.0586 for the Day 10 to Day 20 period, and0.1 for the Day 20 to Day 45 period and for the greater than Day 75period. Although the stored values for 1/p₂ and p₃/p₂ are the same forthe Day 0 to Day 5 and Day 5 to Day 10 periods and for the Day 20 to Day45 and greater than Day 75 periods in the non-limiting examples setforth above, this is not required, and, in some non-limiting alternativeembodiments, the stored values for one or more of 1/p₂ and p₃/p₂ may bedifferent in each of the periods. In addition, some non-limitingalternative embodiments, instead of storing values for one or more of1/p₂ and p₃/p₂, the memory may store different values for one or more ofp₂ and p₃.

In some non-limiting embodiments, the transceiver 101 may update one ormore of the lag parameters to be lag parameters associated with a timeperiod into which the life of the analyte sensor 100 has entered. Insome embodiments, after updating the lag parameters, the calibrationprocess 700 may proceed from step 714 back to step 702. In someembodiments, the transceiver 101 may then use a conversion function withthe one or more updated lag parameters when calculating one or moresubsequent sensor measurements SM1 (e.g., when the transceiver 101performs step 704 after received additional sensor data in step 702).

In some embodiments, in step 712, if the transceiver 101 does notdetermine that one or more lag parameters should be updated, thecalibration process 700 may proceed back to step 702, and thecalibration process 700 may continue without updating any lag parametersand using the current conversion function to calculate sensormeasurements when sensor data is received until a reference measurementRM1 is received (or the lag parameters are updated).

In some non-limiting embodiments, the calibration process 700 mayinclude a step 708 in which the reference measurement RM1 is stored in,for example, a calibration point memory (e.g., a circular buffer). Insome embodiments, the reference measurement RM1 may be stored in thecalibration point memory with a corresponding reference time stamp. Asexplained above, in some embodiments, the reference time stamp mayindicate the time at which a user entered the reference measurement RM1(either into the display device 105 or the into the transceiver 101),the time at which the reference measurement was taken (e.g., the time atwhich blood was drawn for an SMBG measurement), or the time at which thetransceiver 101 received the reference measurement from the displaydevice 105. In some embodiments, the calibration process 700 may proceeddirectly from step 708 to a step 710 (and the process 700 may notinclude dynamic lag parameter update steps 716 and 718). In somenon-limiting alternative embodiments, as illustrated in FIG. 9, thecalibration process 700 may include dynamic lag parameter update steps716 and 718, and the calibration process 700 may proceed from step 708to the step 716.

In some embodiments, the calibration process 700 may include a step 716in which the transceiver 101 determines whether to update dynamicallyone or more lag parameters (e.g., one or more of 1/p₂ and p₃/p₂ or oneor more of the analyte diffusion rate p₂ and the analyte consumptionrate p₃). In some embodiments, the transceiver 101 may determine that nodynamic update is needed if only one reference measurement RM1 has beenstored in the calibration point memory (i.e., if the referencemeasurement RM1 stored in step 708 was the first calibration point). Insome embodiments, the transceiver 101 may additionally or alternativelydetermine that no dynamic update is needed if one or more of the lagparameters were updated recently (e.g., in step 714). In somenon-limiting embodiments, one or more of the lag parameters may havebeen updated recently if the reference measurement RM1 most recentlyreceived and stored in the calibration point memory is the firstcalibration point received and stored since updating one or more of thelag parameters in step 714. For example and without limitation, innon-limiting some embodiments, one or more of the lag parameters mayhave been updated recently if the reference measurement RM1 mostrecently received and stored in the calibration point memory is thefirst reference measurement RM1 stored in the calibration point receivedand stored during the current time period (e.g., the current one of thefollowing six time periods: (1) Day 0 to Day 5, (2) Day 5 to Day 10, (3)Day 10 to Day 20, (4) Day 20 to Day 45, (5) Day 45 to Day 75, and (6)greater than Day 75). In some embodiments, if the transceiver 101determines in step 716 that no dynamic update is needed, the process 700may proceed from step 716 to a calibration step 710. However, if thetransceiver 101 determines in step 716 to update dynamically one or morelag parameters, the process 700 may proceed from step 716 to a dynamiclag parameter update step 718.

In some embodiments, the calibration process 700 may include a dynamiclag parameter update step 718 in which the transceiver 101 updatesdynamically one or more of the lag parameters of the analyte transportmodel. In some embodiments, the lag parameters may be L1 and L2. In someembodiments, lag parameters L1 and L2 may be 1/p₂ and p₃/p₂,respectively. In some alternative embodiments, L1 and L2 may be theanalyte diffusion rate p₂ and the analyte consumption rate p₃,respectively.

In some embodiments, the transceiver 101 may characterize accuracy usingone or more reference measurements stored in the calibration pointmemory. In some non-limiting embodiments, the transceiver 101 maycharacterize accuracy using the most recent reference measurements(e.g., the most-recent 10 reference measurements). In some non-limitingembodiments, the transceiver 101 may use the recent referencemeasurements in a weighted fashion. In some non-limiting embodiments,the transceiver 101 may update the lag parameters using the lagparameters that most accurately fit the most recent referencemeasurements.

In some non-limiting embodiments, the transceiver 101 may update one ormore of the lag parameters L1 and L2 using a two parameter (Mop andNMop) method. In some non-limiting embodiments, the two parameter methodmay use a Minimal Deviation Divergence Method (MDDM) to determine theparameters with the best fit and minimal divergence from the previousparameters. In some non-limiting embodiments, in the two parametermethod with MDDM, at calibration time t_(n), let Mop(t_(n))=L1(t _(n))and NMop(t_(n))=L2(t _(n)). In some embodiments, the two parametermethod with MDDM may include obtaining N candidate Mop and NMop valuesbased on their previous values and the search step specified in a sensorcalibration file. In one non-limiting example, N may be equal to 20, thesearch steps may be 50 for Mop and 0.1 for NMop, the actual parameterincremental step may be calculated as (50+50)/20=5 for Mop and(0.1+0.1)/20=0.01 for NMop, and the resulting candidate Mop and NMopvalues may be:

NMop_(try(t_(n), 1)) = NMop(t_(n − 1)) − 0.1NMop_(try(t_(n), 2)) = NMop(t_(n − 1)) − 0.1 + 0.01NMop_(try(t_(n), 3)) = NMop(t_(n − 1)) − 0.1 + 0.02 ⋮NMop_(try(t_(n), i)) = NMop(t_(n − 1)) − 0.1 + 0.01 * (i − 1) ⋮NMop_(try(t_(n), 20)) = NMop(t_(n − 1)) − 0.1 + 0.19 andMop_(try(t_(n), 1)) = Mop(t_(n − 1)) − 50Mop_(try(t_(n), 2)) = Mop(t_(n − 1)) − 50 + 5Mop_(try(t_(n), 3)) = Mop(t_(n − 1)) − 50 + 10 ⋮Mop_(try(t_(n), j)) = Mop(t_(n − 1)) − 50 + 5 * (j − 1) ⋮Mop_(try(t_(n), 20)) = Mop(t_(n − 1)) − 50 + 95However, the exact values used in the non-limiting examples set forthabove are not required, and, in some alternative embodiments, one ormore of N, the search step for Mop, and the search step for NMop may bedifferent.

In some embodiments, in updating on or more of the lag parameters, thetransceiver 101 may apply an upper and lower boundary for NMop and Mop.For example, if NMop-0.1<LB_NMop, NMop_(try(t_n,1)) may be LB_NMopinstead (that is, NMop_(try(t) _(n) _(,1))=LB_NMop). The same may applyto the upper boundary and Mop. In some non-limiting embodiments, one ormore of the boundaries may be saved (e.g., in a sensor calibration file)as a percentage relative to the fixed lag parameters in that period.

In some embodiments, weights for up to a number of referencemeasurements (e.g., up to 10 SMBGs) in the buffer may be calculated asbelow:

${{{Weight}\left( t_{n - i} \right)} = {\exp\left( \frac{t_{n} - t_{n - i}}{weightTimeConstantSeconds} \right)}},$where i=0 to 9, and weightTimeConstantSeconds is a parameter in thecalibration file. In some non-limiting embodiments,weightTimeConstantSeconds may be specified as t_(n)-t_(n-1).

For each NMop_(try) and Mop_(try) combination, BG is calculatedaccording to (1) and the residual and deviation are defined as below:

${{{Residual}\left( {{iNMop}_{try},{jMop}_{try}} \right)} = \sqrt{{\Sigma_{k = 0}^{9}\left\lbrack {{{Weight}\left( t_{n - k} \right)}*{{weightedMARD}\left( t_{n - k} \right)}} \right\rbrack}^{2}}},{{{where}\mspace{14mu} k} = {1\mspace{14mu}{to}\mspace{14mu} 9}}$${{Deviation}\left( {{iNMop}_{try},{jMop}_{try}} \right)} = {{\frac{{{{NMop}_{try}\left( {t_{n},{iNMop}_{try}} \right)} - {{NMop}\left( t_{n - 1} \right)}}}{0.1} + {\frac{{{{Mop}_{try}\left( {t_{n},{jMop}_{try}} \right)} - {{Mop}\left( t_{n - 1} \right)}}}{50}.{{weightedMARD}\left( t_{n} \right)}}} = \left\{ {\begin{matrix}{\frac{{{{BG}\left( t_{n} \right)} - {{FS}\left( t_{n} \right)}}}{{FS}\left( t_{n} \right)},{{{if}\mspace{14mu}{{FS}\left( t_{n} \right)}} \geq {hypoglycemiaThresholdMgDl}}} \\{\frac{{{{BG}\left( t_{n} \right)} - {{FS}\left( t_{n} \right)}}}{hypoglycemiaThresholdMgDl},{{{if}\mspace{14mu}{{FS}\left( t_{n} \right)}} < {hypoglycemiaThresholdMgDl}}}\end{matrix},} \right.}$where FS is the reference measurement or calibration point (e.g., anSMBG measurement). In some non-limiting alternative embodiments, theequation above for Residual(iNMop_try,jMop_try) may additionally includea time domain weight v(t_(n-k)). See paragraphs 0099-0101 below foradditional information regarding the time domain weight.

In some non-limiting embodiments, in the dynamic lag parameter updatestep 718, the transceiver 101 may find all the NMop_(try) and Mop_(try)combinations with a Residual within 105% (can change) of the minimalResidual, and select the NMop_(try) and Mop_(try) combination with theminimal Deviation as the updated lag parameters L₂ and L₁. The updatedL₂ and L₁ may be saved in the calibration point memory (e.g., a circularbuffer) and used for lag compensation until the next calibration point(i.e., until the next reference measurement RM1 is received in step 706and stored in step 708).

In some embodiments, in the dynamic lag parameter update step 718, thetransceiver 101 may use one or more of first and second methods toupdate the lag parameters L1 and L2 during first and second periods,respectively. In some non-limiting embodiments, the first method may bethe ratio method. In some non-limiting embodiments, the second methodmay be the two parameter method. In some non-limiting embodiments, theratio method may determine a value MF1 that describes the relationshipbetween baseline fluorescence of the analyte indicator element 106 and achange in sensor opacity that occurs with hydration. In someembodiments, the ratio method may use MDDM to determine the parameterwith the best fit and minimal divergence from the previous parameter.

In some non-limiting embodiments, in the dynamic lag parameter updatestep 718, the transceiver 101 may use the first and second methods toupdate the lag parameters L1 and L2 during first and second periods,respectively. For example, in some non-limiting embodiments, thetransceiver 101 may use the first method to estimate the updated lagparameters during the first period and may use the second method toestimate the updated lag parameters during the second period. In somenon-limiting embodiments, the first period may be the period from sensorinsertion until a predetermined amount of time (such as, for example andwithout limitation, 10 days) has passed. In some alternativeembodiments, the first period may be the period from sensor insertionuntil the time at which the second method becomes more accurate than thefirst method (e.g., as determined by comparing sensor measurementscalculated using the first and second methods with received referencemeasurements). In some non-limiting embodiments, the second period maybegin when the first period ends. In some non-limiting embodiments, thesecond period may continue until the end of sensor life, but this is notrequired. In some alternative embodiments, the second period may endafter a predetermined amount of time, and the transceiver 101 may use athird method to estimate the updated lag parameters during a thirdperiod of time that begins when the second period ends.

In some alternative embodiments, in the dynamic lag parameter updatestep 718, the transceiver 101 may use the first and second methodssimultaneously (instead of sequentially) to update the lag parameters L1and L2. For example, in some alternative embodiments, the transceiver101 may estimate (i) a first set of updated lag parameters using thefirst method and (ii) a second set of updated lag parameters using thesecond method. The transceiver 101 may calculate sensor measurementsusing both the first and second sets of updated lag parameters. Thetransceiver 101 may evaluate the calculated sensor measurements foraccuracy by comparing them to one or more reference measurements (e.g.,one or more self-monitoring blood glucose (SHBG) measurements such as,for example and without limitation, one or more finger-stickmeasurements). The transceiver 101 may select the more accuratecalculated sensor measurements for display to the user.

In some embodiments, as shown in FIG. 9, the process 700 may proceedfrom dynamic lag parameter update step 718 to a calibration step 710.

In some embodiments, the calibration process 700 may include a step 710in which the transceiver 101 may calibrate the conversion function usedto calculate blood analyte measurements from sensor data. In somenon-limiting embodiments, the transceiver 101 may calibrate theconversion function using one or more of the calibration points storedin the calibration point memory. In some embodiments, the one or morecalibration points used to calibrate the conversion function may includethe reference measurement RM1. In some non-limiting embodiments, thetransceiver 101 may assign weights to the one or more calibrationpoints.

In some non-limiting embodiments, in step 710, the transceiver 101 mayassign weights to the one or more calibration points according to, forexample and without limitation, a weighted average cost function. Insome non-limiting embodiments, the weighted average cost function may,for example and without limitation, have the following form:

${{cost}\mspace{14mu}{function}} = \sqrt{\sum\limits_{i = {- {({N - 1})}}}^{0}\;\left( {w_{i}*v_{i}*{{Error}(\theta)}_{i}} \right)^{2}}$

In some embodiments, in the weighted average cost function set forthabove, 0 may be one or more calibration parameters, w_(i) may be a timedomain weight for the calibration point, v_(i) may be an analyteconcentration domain weight for the calibration point, and Error(θ)_(i)may be an accuracy metric between the SMBG calibration points and thecalculated sensor analyte concentration (SM1).

In some embodiments, the time domain weight, w_(i), may be calculated inthe following manner:

${w_{i} = {\exp\left( \frac{t_{i} - t_{0}}{\lambda} \right)}},{i = {- \left( {N - 1} \right)}},{- \left( {N - 2} \right)},{\ldots\mspace{14mu} 0}$In these embodiments, t₀ may be the time stamp of the currentcalibration point, t_(−(N-1)), t_(−(N-2)), . . . , t⁻¹ may be timestamps for previous N−1 calibration points, and λ, may be a relativetime difference between the current and the previous calibration points,t₀-t⁻¹. In some embodiments, λ may be a constant such as, for exampleand without limitation, 111328 seconds. In some embodiments, N may be aconstant such as, for example and without limitation, 10. However, thesespecific values of λ and N are not required, and, in some alternativeembodiments, different values may be used for one or more of λ and N.

In some non-limiting embodiments, the transceiver 101 may assign weightsbased on the age of the calibration points with less weight being givento older calibration points (e.g., in accordance with the weightedaverage cost function described above). However, this is not required,and the transceiver 101 may assign weights to the calibration pointsbased on other computational or analytical methodologies.

In some embodiments, the calibration step 710 may include pairing one ormore of the calibration points stored in the calibration point memory,which may include the reference measurement RM1, with one or more of thesensor measurements SM1 calculated in step 704. In some embodiments, thetransceiver 101 may pair a calibration point with the sensor measurementSM1 having a time stamp closest to the time stamp of the calibrationpoint. In some alternative embodiments, the transceiver 101 may pair acalibration point with an interpolated sensor measurement value if nosensor measurement SM1 has a time stamp that exactly matches the timestamp of the calibration point. That is, in some alternativeembodiments, if the time stamp of the calibration point is in-betweenthe time stamps of the sensor measurements SM1, the transceiver may pairthe calibration point with an interpolated sensor measurement value. Insome non-limiting embodiments, the transceiver 101 may use a sub-set orall of the sensor measurements SM1 and their time stamps to interpolatea sensor measurement value corresponding to the time stamp for thereference measurement RM1. In some non-limiting embodiments, theinterpolation may be, for example and without limitation, linearinterpolation, polynomial interpolation, or spline interpolation.

In some embodiments, the calibration process 700 may proceed from step710 to step 702, and the transceiver 101 may use the updated conversionfunction to calculate blood analyte measurements from subsequent sensordata.

Embodiments of the present invention have been fully described abovewith reference to the drawing figures. Although the invention has beendescribed based upon these preferred embodiments, it would be apparentto those of skill in the art that certain modifications, variations, andalternative constructions could be made to the described embodimentswithin the spirit and scope of the invention. For example, although theinvention is described above in the context of an analyte monitoringsystem that calculates blood analyte levels indirectly usingmeasurements of analyte levels in interstitial fluid, the invention isapplicable to any monitoring system that calculates levels in a firstmedium using measurements of levels in a second medium.

What is claimed is:
 1. A method of calculating an analyte level in afirst medium using one or more measurements of an analyte level in asecond medium, the method comprising: receiving first sensor data froman analyte sensor; calculating a first analyte level in the secondmedium using at least the first sensor data; calculating a first analytelevel rate of change using at least the first analyte level in thesecond medium; calculating a first analyte level in the first mediumusing at least the first analyte level in the second medium, the firstanalyte level rate of change, and one or more lag parameters;determining that the one or more lag parameters should be updated;updating the one or more lag parameters; receiving second sensor datafrom the analyte sensor; calculating a second analyte level in thesecond medium using at least the second sensor data; calculating asecond analyte level rate of change using at least the second analytelevel in the second medium; and calculating a second analyte level inthe first medium using at least the second analyte level in the secondmedium, the second analyte level rate of change, and the updated one ormore lag parameters; wherein the one or more lag parameters include oneor more of an analyte diffusion rate and an analyte consumption rate. 2.The method of claim 1, wherein the first medium is blood, and the secondmedium is interstitial fluid.
 3. The method of claim 1, furthercomprising determining whether to dynamically update one or more of thelag parameters.
 4. The method of claim 3, further comprising dynamicallyupdating one or more of the lag parameters.
 5. The method of claim 4,wherein dynamically updating one or more of the lag parameters comprisesusing a minimum deviation divergence method.
 6. The method of claim 1,further comprising dynamically updating one or more of the lagparameters.
 7. A method of calculating an analyte level in a firstmedium using one or more measurements of an analyte level in a secondmedium, the method comprising: receiving first sensor data from ananalyte sensor; calculating a first analyte level in the second mediumusing at least the first sensor data; calculating a first analyte levelrate of change using at least the first analyte level in the secondmedium; calculating a first analyte level in the first medium using atleast the first analyte level in the second medium, the first analytelevel rate of change, and one or more lag parameters; determining thatthe one or more lag parameters should be updated, wherein determiningthat the one or more lag parameters should be updated comprisesdetermining that a period of time has passed since the one or more ofthe lag parameters have been updated; updating the one or more lagparameters; receiving second sensor data from the analyte sensor;calculating a second analyte level in the second medium using at leastthe second sensor data; calculating a second analyte level rate ofchange using at least the second analyte level in the second medium; andcalculating a second analyte level in the first medium using at leastthe second analyte level in the second medium, the second analyte levelrate of change, and the updated one or more lag parameters.
 8. Themethod of claim 7, wherein the one or more lag parameters include one ormore of an analyte diffusion rate and an analyte consumption rate.
 9. Amethod of calculating an analyte level in a first medium using one ormore measurements of an analyte level in a second medium, the methodcomprising: receiving first sensor data from an analyte sensor;calculating a first analyte level in the second medium using at leastthe first sensor data; calculating a first analyte level rate of changeusing at least the first analyte level in the second medium; calculatinga first analyte level in the first medium using at least the firstanalyte level in the second medium, the first analyte level rate ofchange, and one or more lag parameters, wherein calculating the firstanalyte level in the first medium comprises employing an asymmetricallag methodology; determining that the one or more lag parameters shouldbe updated; updating the one or more lag parameters; receiving secondsensor data from the analyte sensor; calculating a second analyte levelin the second medium using at least the second sensor data; calculatinga second analyte level rate of change using at least the second analytelevel in the second medium; and calculating a second analyte level inthe first medium using at least the second analyte level in the secondmedium, the second analyte level rate of change, and the updated one ormore lag parameters.
 10. The method of claim 9, wherein the asymmetricallag approach decelerates a rate of change of falling analyte levelsduring a low blood analyte event and accelerates a rate of change ofincreasing analyte levels during recovery from the low blood analyteevent.
 11. A method of calculating an analyte level in a first mediumusing one or more measurements of an analyte level in a second medium,the method comprising: receiving first sensor data from an analytesensor; calculating a first analyte level in the second medium using atleast the first sensor data; calculating a first analyte level rate ofchange using at least the first analyte level in the second medium;calculating a first analyte level in the first medium using at least thefirst analyte level in the second medium, the first analyte level rateof change, and one or more lag parameters; determining that the one ormore lag parameters should be updated; updating the one or more lagparameters, wherein updating the one or more lag parameters comprisesusing one or more of a first method and a second method to estimate oneor more updated lag parameters; receiving second sensor data from theanalyte sensor; calculating a second analyte level in the second mediumusing at least the second sensor data; calculating a second analytelevel rate of change using at least the second analyte level in thesecond medium; and calculating a second analyte level in the firstmedium using at least the second analyte level in the second medium, thesecond analyte level rate of change, and the updated one or more lagparameters.
 12. The method of claim 11, wherein the first method is aratio method.
 13. The method of claim 11, wherein the second method is atwo-parameter method.
 14. The method of claim 11, wherein updating oneor more lag parameters comprises using the first method during a firstperiod and using the second method during a second period.
 15. Themethod of claim 11, wherein updating one or more lag parameterscomprises using both the first and second methods.
 16. The method ofclaim 15, wherein using both the first and second methods comprises:using the first method to estimate a first set of updated lagparameters; using the second method to estimate a second set of updatedlag parameters; using the first set of updated lag parameters tocalculate one or more first sensor measurements; using the second set ofupdated lag parameters to calculate one or more second sensormeasurements; evaluating the one or more first sensor measurements andthe one or more second sensor measurements by comparing the one or morefirst sensor measurements and the one or more second sensor measurementsto one or more reference measurements; and selecting the more accurateof (a) the one or more first sensor measurements and (b) the one or moresecond sensor measurements for display to a user.
 17. An analytemonitoring system comprising: an analyte sensor including an indicatorelement that exhibits one or more detectable properties based on aconcentration of an analyte in proximity to the indicator element; and atransceiver configured to: receive first sensor data from the analytesensor; calculate a first analyte level in the second medium using atleast the first sensor data; calculate a first analyte level rate ofchange using at least the first analyte level in the second medium;calculate a first analyte level in the first medium using at least thefirst analyte level in the second medium, the first analyte level rateof change, and one or more lag parameters; determine that the one ormore lag parameters should be updated; update the one or more lagparameters; receive second sensor data from the analyte sensor;calculate a second analyte level in the second medium using at least thesecond sensor data; calculate a second analyte level rate of changeusing at least the second analyte level in the second medium; calculatea second analyte level in the first medium using at least the secondanalyte level in the second medium, the second analyte level rate ofchange, and the updated one or more lag parameters; wherein the one ormore lag parameters include one or more of an analyte diffusion rate andan analyte consumption rate.
 18. The analyte monitoring system of claim17, wherein the first medium is blood, and the second medium isinterstitial fluid.
 19. The analyte monitoring system of claim 17,wherein the transceiver is further configured to determine whether todynamically update one or more of the lag parameters.
 20. The analytemonitoring system of claim 19, wherein the transceiver is furtherconfigured to dynamically update one or more of the lag parameters. 21.The analyte monitoring system of claim 20, wherein dynamically updatingone or more of the lag parameters comprises using a minimum deviationdivergence method.
 22. The analyte monitoring system of claim 17,wherein the transceiver is further configured to dynamically update oneor more of the lag parameters.
 23. An analyte monitoring systemcomprising: an analyte sensor including an indicator element thatexhibits one or more detectable properties based on a concentration ofan analyte in proximity to the indicator element; and a transceiverconfigured to: receive first sensor data from the analyte sensor;calculate a first analyte level in the second medium using at least thefirst sensor data; calculate a first analyte level rate of change usingat least the first analyte level in the second medium; calculate a firstanalyte level in the first medium using at least the first analyte levelin the second medium, the first analyte level rate of change, and one ormore lag parameters; determine that the one or more lag parametersshould be updated, wherein determining that the one or more lagparameters should be updated comprises determining that a period of timehas passed since the one or more of the lag parameters have beenupdated; update the one or more lag parameters; receive second sensordata from the analyte sensor; calculate a second analyte level in thesecond medium using at least the second sensor data; calculate a secondanalyte level rate of change using at least the second analyte level inthe second medium; and calculate a second analyte level in the firstmedium using at least the second analyte level in the second medium, thesecond analyte level rate of change, and the updated one or more lagparameters.
 24. The analyte monitoring system of claim 23, wherein theone or more lag parameters include one or more of an analyte diffusionrate and an analyte consumption rate.
 25. An analyte monitoring systemcomprising: an analyte sensor including an indicator element thatexhibits one or more detectable properties based on a concentration ofan analyte in proximity to the indicator element; and a transceiverconfigured to: receive first sensor data from the analyte sensor;calculate a first analyte level in the second medium using at least thefirst sensor data; calculate a first analyte level rate of change usingat least the first analyte level in the second medium; calculate a firstanalyte level in the first medium using at least the first analyte levelin the second medium, the first analyte level rate of change, and one ormore lag parameters, wherein calculating the first analyte level in thefirst medium comprises employing an asymmetrical lag methodology;determine that the one or more lag parameters should be updated; updatethe one or more lag parameters; receive second sensor data from theanalyte sensor; calculate a second analyte level in the second mediumusing at least the second sensor data; calculate a second analyte levelrate of change using at least the second analyte level in the secondmedium; and calculate a second analyte level in the first medium usingat least the second analyte level in the second medium, the secondanalyte level rate of change, and the updated one or more lagparameters.
 26. The analyte monitoring system of claim 25, wherein theasymmetrical lag approach decelerates a rate of change of fallinganalyte levels during a low blood analyte event and accelerates a rateof change of increasing analyte levels during recovery from the lowblood analyte event.
 27. An analyte monitoring system comprising: ananalyte sensor including an indicator element that exhibits one or moredetectable properties based on a concentration of an analyte inproximity to the indicator element; and a transceiver configured to:receive first sensor data from the analyte sensor; calculate a firstanalyte level in the second medium using at least the first sensor data;calculate a first analyte level rate of change using at least the firstanalyte level in the second medium; calculate a first analyte level inthe first medium using at least the first analyte level in the secondmedium, the first analyte level rate of change, and one or more lagparameters; determine that the one or more lag parameters should beupdated; update the one or more lag parameters, wherein updating the oneor more lag parameters comprises using one or more of a first method anda second method to estimate one or more updated lag parameters; receivesecond sensor data from the analyte sensor; calculate a second analytelevel in the second medium using at least the second sensor data;calculate a second analyte level rate of change using at least thesecond analyte level in the second medium; and calculate a secondanalyte level in the first medium using at least the second analytelevel in the second medium, the second analyte level rate of change, andthe updated one or more lag parameters.
 28. The analyte monitoringsystem of claim 27, wherein the first method is a ratio method.
 29. Theanalyte monitoring system of claim 27, wherein the second method is atwo-parameter method.
 30. The analyte monitoring system of claim 27,wherein updating one or more lag parameters comprises using the firstmethod during a first period and using the second method during a secondperiod.
 31. The analyte monitoring system of claim 27, wherein updatingone or more lag parameters comprises using both the first and secondmethods.
 32. The analyte monitoring system of claim 31, wherein usingboth the first and second methods comprises: using the first method toestimate a first set of updated lag parameters; using the second methodto estimate a second set of updated lag parameters; using the first setof updated lag parameters to calculate one or more first sensormeasurements; using the second set of updated lag parameters tocalculate one or more second sensor measurements; evaluating the one ormore first sensor measurements and the one or more second sensormeasurements by comparing the one or more first sensor measurements andthe one or more second sensor measurements to one or more referencemeasurements; and selecting the more accurate of (a) the one or morefirst sensor measurements and (b) the one or more second sensormeasurements for display to a user.
 33. A method of calculating ananalyte level in a first medium using one or more measurements of ananalyte level in a second medium, the method comprising: receiving firstsensor data from an analyte sensor; calculating a first analyte level inthe second medium using at least the first sensor data; calculating afirst analyte level rate of change using at least the first analytelevel in the second medium; calculating a first analyte level in thefirst medium using at least the first analyte level in the secondmedium, the first analyte level rate of change, and a first set of oneor more lag parameters; calculating a second analyte level in the firstmedium using at least the first analyte level in the second medium, thefirst analyte level rate of change, and a second set of one or more lagparameters; comparing the first analyte level in the first medium to atleast a reference measurement; comparing the second analyte level in thefirst medium to at least the reference measurement; and selectingwhichever of the first analyte level in the first medium and the secondanalyte level in the first medium is closer to the reference measurementfor display to a user.
 34. An analyte monitoring system comprising: ananalyte sensor including an indicator element that exhibits one or moredetectable properties based on a concentration of an analyte inproximity to the indicator element; and a transceiver configured to:receive first sensor data from the analyte sensor; calculate a firstanalyte level in the second medium using at least the first sensor data;calculate a first analyte level rate of change using at least the firstanalyte level in the second medium; calculate a first analyte level inthe first medium using at least the first analyte level in the secondmedium, the first analyte level rate of change, and a first set of oneor more lag parameters; calculate a second analyte level in the firstmedium using at least the first analyte level in the second medium, thefirst analyte level rate of change, and a second set of one or more lagparameters; compare the first analyte level in the first medium to atleast a reference measurement; compare the second analyte level in thefirst medium to at least the reference measurement; and select whicheverof the first analyte level in the first medium and the second analytelevel in the first medium is closer to the reference measurement fordisplay to a user.